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The hallmark of enthesis architecture is the 3D compositional and structural gradient encompassing four tissue zones - tendon/ligament, uncalcified fibrocartilage, calcified fibrocartilage and bone. This functional gradient accommodates the large stiffness differential between calcified bone and uncalcified tendon/ligament. Here we analyze in 3D the organization of the mouse Achilles enthesis and mineralizing Achilles tendon in comparison to lamellar bone. We use correlative, multiscale high-resolution volume imaging methods including μCT with submicrometer resolution and FIB-SEM tomography (both with deep learning-based image segmentation), and TEM and SEM imaging, to describe ultrastructural features of physiologic, age-related and aberrant mineral patterning. We applied these approaches to murine wildtype (WT) Achilles enthesis tissues to describe in normal calcifying fibrocartilage a crossfibrillar mineral tessellation pattern similar to that observed in lamellar bone, but with greater variance in mineral tesselle morphology and size. We also examined Achilles enthesis structure in Hyp mice, a murine model for the inherited osteomalacic disease X-linked hypophosphatemia (XLH) with calcifying enthesopathy. In Achilles enthesis fibrocartilage of Hyp mice, we show defective crossfibrillar mineral tessellation similar to that which occurs in Hyp lamellar bone. At the cellular level in fibrocartilage, unlike in bone where enlarged osteocyte mineral lacunae are found as peri-osteocytic lesions, mineral lacunar volumes for fibrochondrocytes did not differ between WT and Hyp mice. While both WT and Hyp aged mice demonstrate Achilles tendon midsubstance ectopic mineralization, a consistently defective mineralization pattern was observed in Hyp mice. Strong immunostaining for osteopontin was observed at all mineralization sites examined in both WT and Hyp mice. Taken together, this new 3D ultrastructural information describes details of common mineralization trajectories for enthesis, tendon and bone, which in Hyp/XLH are defective., Competing Interests: Declaration of competing interest All authors indicate that they have no disclosures to make, or any conflicts of interest pertaining to this work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetics and differential diagnoses of fibrocartilaginous lipomas which consist of adipose tissue, fibrocartilage and fibrous elements. Methods: The clinicopathological features, immunohistochemical profiles and molecular profiles in six cases of fibrocartilaginous lipomas diagnosed at Foshan Traditional Chinese Medicine Hospital, Fudan University Shanghai Cancer Center, the Fifth Affiliated Hospital of Zhengzhou University and the Fourth Affiliated Hospital of Harbin Medical University from January 2017 to February 2022 were included. The follow-up information, diagnosis and differential diagnoses were evaluated. Results: There were three males and three females with a median age of 53 years (range 36-69 years) at presentation. Tumors were located in the extremities, the head and neck region and trunk; and presented as painless masses that were located in the subcutaneous tissue or deep soft tissue. Grossly, three cases were well defined with thin capsule, one case was well circumscribed without capsule, two cases were surrounded by some skeletal muscle. The tumors were composed of fatty tissue with intermingled gray-white area. The tumors ranged from 1.50-5.50 cm (mean 2.92 cm). Microscopically, the hallmark of these lesions was the complex admixture of mature adipocytes, fibrocartilage and fibrous element in varying proportions; the fibrocartilage arranged in a nodular, sheet pattern with some adipocytes inside. Tumor cells had a bland appearance without mitotic activity. Immunohistochemical analysis using antibodies to SMA, desmin, S-100, SOX9, HMGA2, RB1, CD34, adipopholin was performed in six cases; the fibrocartilage was positive for S-100 and SOX9, adipocytes were positive for S-100, adipopholin and HMGA2; CD34 was expressed in the fibroblastic cells, while desmin and SMA were negative. Loss of nuclear RB1 expression was not observed. Other genetic abnormalities had not been found yet in four cases. Follow-up information was available in six cases; there was no recurrence in five, and one patient only underwent biopsy of the mass. Conclusions: Fibrocartilaginous lipoma is a benign lipomatous tumor with mature adipocytes, fibrocartilage and fibrous elements. By immunohistochemistry, they show the expression of fat and cartilage markers. No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.

Objective: Osteochondroma is a common benign skeletal disorder for which different molecular and histological features of long bones have been reported. We investigated cell-of-origin and molecular mechanisms of a rare condylar osteochondroma (CO)., Methods: Human fibrocartilage stem cells (hFCSCs) isolated from CO and normal condyle tissue were used for RNA sequencing, real-time PCR, Western Blotting, immunohistology, flowcytometry, as well as for chondrogenic differentiation, proliferation, and apoptosis detection assays., Results: HFCSCs were fewer in number with weaker proliferative capacity and higher apoptosis ratio in the CO group. During the chondrogenic inducing process, hFCSCs from CO were prone to form more mature and hypertrophic cartilage. The result of RNA sequencing of hFCSCs from CO and normal condyle revealed a correlation between the PI3K/AKT signalling pathway and CO. Activated PI3K/AKT signalling might lead to functional changes in hFCSCs by enhancing cell apoptosis in the developmental process of CO. Increased expression of BCL2-like protein 11 (BIM) in CO tissue also supports this conclusion. Furthermore, the activation of the PI3K/AKT pathway in TMJ of mice induced histological disorder and increased apoptosis in condylar cartilage., Conclusion: We conclude that the activation of PI3K/AKT signalling in hFCSCs of CO suggests a new hypothesis for the cell-of-origin of human CO and another possible target to treat it., (© 2022 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

In this study, we investigate harnessing fibrocartilage stem cell (FCSC) capacities by regulating tumor necrosis factor α (TNF-α) signaling for cartilage repair in temporomandibular joint osteoarthritis (TMJOA). Stem cell specifics for FCSCs were characterized in the presence of TNF-α. Etanercept as a TNF-α inhibitor and BAY 11-7082 as an Nf-κB inhibitor were used to study TNF-α regulation of FCSCs. Lineage tracing was performed in Gli1-CreERT + ;Tm fl/fl mice when etanercept (1 mg/kg, every 3 d) or isometric vehicle was subcutaneously injected to trace specific changes in FCSCs. Surgically induced TMJOA Sprague-Dawley rats were generated with BAY 11-7082 (5 mg/kg, every 3 d) or vehicle subcutaneous injection to investigate the functional role of TNF-α/Nf-κB in TMJOA. Anterior disc displacement (ADD) rabbits were used to analyze the therapeutic effect of etanercept as a TMJOA intra-articular treatment with etanercept (0.02 mg in 100 μL, every 2 wk) or isometric vehicle. In vitro, TNF-α inhibited proliferation of FCSCs and increased FCSC apoptosis. TNF-α activation interfered with osteogenic and chondrogenic differentiation of FCSCs, while etanercept could partially recover FCSC specificity from TNF-α. FCSC lineage tracing in Gli1-CreERT + ;Tm fl/fl mice showed that the chondrogenic capacity of Gli1 + cell lineage was markedly suppressed in osteoarthritis cartilage, the phenotype of which could be significantly rescued by etanercept. Specifically blocking the Nf-κB pathway could significantly weaken the regulatory effect of TNF-α on FCSC specificity in vitro and in TMJOA rats in vivo. Finally, intra-articular etanercept treatment efficiently rescued TMJ cartilage degeneration and growth retardation in ADD rabbits. Inhibition of TNF-α signaling reduced Nf-κB transcripts and recovered FCSC specificities. In vivo, etanercept treatment effectively rescued the osteoarthritis phenotype in TMJOA mice and ADD rabbits. These data suggest a novel therapeutic mechanism whereby TNF-α/Nf-κB inhibition promotes FCSC chondrogenic capacity for cartilage transformation in TMJOA.

Introduction: Regeneration of fibrochondrocytes is essential for the healing of the tendon-bone interface (TBI), which is similar to the formation of neurogenic heterotopic ossification (HO). Through single-cell integrative analysis, this study explored the homogeneity of HO cells and fibrochondrocytes., Methods: This study integrated six datasets, namely, GSE94683, GSE144306, GSE168153, GSE138515, GSE102929, and GSE110993. The differentiation trajectory and key transcription factors (TFs) for HO occurrence were systematically analyzed by integrating single-cell RNA (scRNA) sequencing, bulk RNA sequencing, and assay of transposase accessible chromatin seq. The differential expression and enrichment pathways of TFs in heterotopically ossified tissues were identified., Results: HO that mimicked pathological cells was classified into HO1 and HO2 cell subsets. Results of the pseudo-temporal sequence analysis suggested that HO2 is a differentiated precursor cell of HO1. The analysis of integrated scRNA data revealed that ectopically ossified cells have similar transcriptional characteristics to cells in the fibrocartilaginous zone of tendons. The modified SCENIC method was used to identify specific transcriptional regulators associated with ectopic ossification. Xbp1 was defined as a common key transcriptional regulator of ectopically ossified tissues and the fibrocartilaginous zone of tendons. Subsequently, the CellPhoneDB database was completed for the cellular ligand-receptor analysis. With further pathway screening, this study is the first to propose that Xbp1 may upregulate the Notch signaling pathway through Jag1 transcription. Twenty-four microRNAs were screened and were found to be potentially associated with upregulation of XBP1 expression after acute ischemic stroke., Conclusion: A systematic analysis of the differentiation landscape and cellular homogeneity facilitated a molecular understanding of the phenotypic similarities between cells in the fibrocartilaginous region of tendon and HO cells. Furthermore, by identifying Xbp1 as a hub regulator and by conducting a ligand-receptor analysis, we propose a potential Xbp1/Jag1/Notch signaling pathway., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Yisheng Chen et al.)

The fibrocartilage chondrocyte phenotype has been recognized to attribute to osteoarthritis (OA) development. These chondrocytes express genes related to unfavorable OA outcomes, emphasizing its importance in OA pathology. BMP7 is being explored as a potential disease-modifying molecule and attenuates the chondrocyte hypertrophic phenotype. On the other hand, BMP7 has been demonstrated to relieve organ fibrosis by counteracting the pro-fibrotic TGFβ-Smad3-PAI1 axis and increasing MMP2-mediated Collagen type I turnover. Whether BMP7 has anti-fibrotic properties in chondrocytes is unknown. Human OA articular chondrocytes (HACs) were isolated from end-stage OA femoral cartilage (total knee arthroplasty; n = 18 individual donors). SW1353 cells and OA HACs were exposed to 1 nM BMP7 for 24 h, after which gene expression of fibrosis-related genes and fibrosis-mediating factors was determined by RT-qPCR. In SW1353, Collagen type I protein levels were determined by immunocytochemistry and western blotting. PAI1 and MMP2 protein levels and activity were measured with an ELISA and activity assays, respectively. MMP2 activity was inhibited with the selective MMP-2 inhibitor OA-Hy. SMAD3 activity was determined by a (CAGA) 12 -reporter assay, and pSMAD2 levels by western blotting. Following BMP7 exposure, the expression of fibrosis-related genes was reduced in SW1353 cells and OA HACs. BMP7 reduced Collagen type I protein levels in SW1353 cells. Gene expression of MMP2 was increased in SW1353 cells following BMP7 treatment. BMP7 reduced PAI1 protein levels and -activity, while MMP2 protein levels and -activity were increased by BMP7. BMP7-dependent inhibition of Collagen type I protein levels in SW1353 cells was abrogated when MMP2 activity was inhibited. Finally, BMP7 reduced pSMAD2 levels determined by western blotting and reduced SMAD3 transcriptional activity as demonstrated by decreased (CAGA) 12 luciferase reporter activity. Our data demonstrate that short-term exposure to BMP7 decreases the fibrocartilage chondrocyte phenotype. The BMP7-dependent reduction of Collagen type I protein expression seems MMP2-dependent and inhibition of Smad2/3-PAI1 activity was identified as a potential pathway via which BMP7 exerts its anti-fibrotic action. This indicates that in chondrocytes BMP7 may have a double mode-of-action by targeting both the hypertrophic as well as the fibrotic chondrocyte phenotype, potentially adding to the clinical relevance of using BMP7 as an OA disease-modifying molecule., (© 2021. The Author(s).)

An enthesis refers to the interface at which a tendon or a ligament integrates into the periosteum. Its morphology can be influenced by intrinsic factors such as sex, age, and extrinsic factors such as levels of activity, which will in turn impact on bone remodeling and lead to morphological changes. In bioarcheology, entheseal changes have had a long tradition of being used for the reconstruction of past activities. The literature has shown that in some cases of osteoarthritis, entheseal changes are associated with osteoarthritic manifestations. This work aims to evaluate the relationship between the degree of entheseal changes and the severity of osteodegenerative processes. The studied materials consisted of 30 humeri and 30 femora from the osteological collection at St George's University of London. Intensities of both entheseal changes and osteodegenerative processes were macroscopically assessed and scored. The difference in scores of entheseal changes between osteoarthritic groups and nonosteoarthritic groups is statistically significant at a confidence level of 95% (α = .05) for both the humeri and femora. Results show a positive correlation between the degree of entheseal changes and the severity of osteodegenerative processes in the femora, suggesting that enthesis may play a role in osteoarthritis. Findings from this work supports the proposed hypothesis that the degree of entheseal changes and the severity of osteoarthritic manifestation are related. This work contributes to current knowledge that osteoarthritis is a disease involving the whole joint; the enthesis could potentially be a target for the diagnosis of osteoarthritis., (© 2020 American Association for Anatomy.)

Purpose: This study aimed to investigate how fibroblastic and chondrocytic properties of human meniscal fibrochondrocytes are affected in culture conditions according to the type of meniscal pathology and localization, and to provide basic information for tissue-engineering studies., Methods: Primary fibrochondrocyte cultures were prepared from meniscus samples of patients who had either traumatic tear or degeneration due to osteoarthritis. Cultures were compared in terms of mRNA expression levels of COL1A1, COL2A1, COMP1, HIF1A, HIF2A, and SOX9 and secreted total collagen and sulfated sGAG levels according to the type of meniscal pathology, anatomical localization, and the number of subcultures., Results: mRNA expression levels of COL1A1, COMP1, HIF1A, HIF2A, and SOX9 were found to be increased in subsequent subcultures in all specimens. COL1A1 mRNA expression levels of both lateral and medial menisci of patients with traumatic tear were significantly higher than in patients with degenerative pathology, indicating a more fibroblastic character. P1 subculture of lateral and P3 or further subculture of medial meniscus showed more fibroblastic characteristics in patients with degenerative pathology. Furthermore, in patients with degenerative pathology, the subcultures of the lateral meniscus (especially on the inner part) presented more chondrocytic characteristics than did those of medial meniscus., Conclusions: The mRNA expression levels of the cultures showed significant differences according to the anatomical localization and pathology of the meniscus, indicating distinct chondrocytic and fibroblastic features. This fundamental knowledge would help researchers to choose more efficient cell sources for cell-seeding of a meniscus scaffold, and to generate a construct resembling the original meniscus tissue.

Objectives: To investigate if cartilage calcification (CC) is a systemic process, the purpose of this study was to determine the prevalence and the amount of meniscal/hyaline CC of the knee joint in the general population by high-resolution imaging (DCR) and to evaluate the association between CC with cartilage degeneration and age., Methods: Cross-sectional DCR-study of 180 knee joints of 90 donors (42 female/48 male, mean age 62.3y). Histological hyaline (OARSI) and meniscal (Krenn) cartilage degeneration was determined of all knees., Results: CC was observed in 100% of the donors (bilaterally in 98%), hyaline cartilage calcification (HCC) in 92% and meniscal calcification (MC) in 100%. CC was detected in more than three out of six distinct cartilage areas in 84.4% of all knees. The mean amount of CC correlated between both sides of donors, the different analyzed areas of the knee joint and between the various types of cartilage structures. There was more calcification in meniscal than in hyaline cartilage (factor 5.3) and in the medial than the lateral compartment (factor 1.2). HCC/MC were already detectable with only mild cartilage lesions and the amount correlated with histological cartilage degeneration, but not with age., Conclusions: The present study provides evidence that meniscal and hyaline CC occurs in a pattern that is compatible with CC being a systemically driven process and that meniscal fibrocartilage is more prone to calcification than hyaline cartilage. Furthermore, the age-independent association between the amount of CC and the grade of degeneration in both hyaline and meniscal cartilage, suggests that CC is an obligatory early event in initiating cartilage degeneration., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Numerous reports have shown that retracted rotator cuff tears may cause suprascapular nerve injury, and nerve injury causes atrophy and fat accumulation in the rotator cuff muscles. However, the effect of suprascapular nerve injury on rotator cuff enthesis has not been directly defined. This study aimed to investigate the effect of suprascapular nerve injury on rotator cuff enthesis., Methods: Twenty-four Wistar albino rats underwent bilateral transection of the suprascapular nerve. Additional 6 rats were used as the sham group. Bilateral supraspinatus and infraspinatus entheses were examined after 1, 4, 8, and 12 weeks of nerve transection. Histomorphometric analyses were performed for each zone of enthesis., Results: Compared with normal enthesis, significant and consistent decrease in cellularity were observed in the tendon and bone at all time points (P < .001). Collagen bundle diameter in the tendon also decreased in a similar manner (P < .001). Apart from the tendon and bone zones, fibrocartilage and calcified fibrocartilage zones showed similar response, and significant decrease in cellularity was observed 8 weeks after nerve transection (P < .001)., Conclusion: This study identifies suprascapular nerve injury as an underlying mechanism leading to compromise of the rotator cuff enthesis structure. Suprascapular nerve injury may be considered as an etiologic factor for the impaired healing after repair of a massive tear., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Congenital external auditory canal stenosis (EACS) is a spectrum of abnormalities affecting the external and middle ear. We report a 6 year-old patient with EACS affecting the lateral fibrocartilaginous canal that was successfully repaired. This patient highlights a variant of EACS characterized by lateral soft tissue narrowing with normal osseous development. Most previous studies of CAA have described severe forms associated with complete atresia, bony stenosis, and middle ear malformations. Stenosis affecting only the fibrocartilaginous canal is a milder form resulting from premature arrest of the canalization process during embryologic development, and may predispose to cholesteatoma formation., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Acellular human dermal allograft commonly is used in the surgical treatment of complex rotator cuff tears, but little information is known about the biological fate of these grafts in human subjects. In this case report, the authors describe a patient who presented with a radiographically healed acellular human dermal allograft superior capsular reconstruction but had humeral head avascular necrosis. The healed superior capsular reconstruction, including graft-bone interfaces, was explanted after 7 months and sent for histologic analysis. A successful biological reconstruction of the superior capsule was found. The graft demonstrated gross and microscopic incorporation with the host, including a tendon-like structure, aligned collagen fibers, fibroblast-like cells, and no clear graft-host distinction. Cellular infiltration ranged from 5% to 14% (central graft) to 65% to 92% (sutured attachment points). Neovascularization and active graft remodeling were confirmed histologically. LEVEL OF EVIDENCE: V, case report., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: The spring ligament fibrocartilage complex (SLFC) is an important static foot stabilizer comprising the superomedial ligament (SML) and the inferior ligament, with anatomical variations (third ligament). The aim of this study was to describe the patterns of the lesions found during SLFC surgery, to allow direct comparison between the results with various surgical techniques., Methods: Fourteen consecutive patients with SLFC lesions were analyzed during surgical treatment. The mean patient age was 37.3 years, and the mean time from injury was 6.9 months. Intraoperative assessments and anatomical descriptions of the lesions were collected., Results: Three types of lesion were found. In 13 of 14 cases, only the superomedial ligament was involved: five superomedial ligament distentions and eight superomedial ligament ruptures. In one case, total SLFC (superomedial and inferior ligaments) rupture was observed., Conclusions: The first classification of SLFC lesions is presented, which is simple, consistent, and based on anatomical description.

Purpose of Review: Elucidate temporomandibular joint (TMJ) development and pathophysiology relative to regeneration, degeneration, and adaption., Recent Findings: The pharyngeal arch produces a highly conserved stomatognathic system that supports airway and masticatory function. An induced subperiosteal layer of fibrocartilage cushions TMJ functional and parafunctional loads. If the fibrocartilage disc is present, a fractured mandibular condyle (MC) regenerates near the eminence of the fossa via a blastema emanating from the medial periosteal surface of the ramus. TMJ degenerative joint disease (DJD) is a relatively painless osteoarthrosis, resulting in extensive sclerosis, disc destruction, and lytic lesions. Facial form and symmetry may be affected, but the residual bone is vital because distraction continues to lengthen the MC with anabolic bone modeling. Extensive TMJ adaptive, healing, and regenerative potential maintains optimal, life support functions over a lifetime. Unique aspects of TMJ development, function, and pathophysiology may be useful for innovative management of other joints.

Osteoarthritis (OA), a degenerative joint disease characterized by progressive cartilage degeneration, is one of the leading causes of disability worldwide owing to the limited regenerative capacity of adult articular cartilage. Currently, there are no disease-modifying pharmacological or surgical therapies for OA. Fetal mammals, in contrast to adults, are capable of regenerating injured cartilage in the first two trimesters of gestation. A deeper understanding of the properties intrinsic to the response of fetal tissue to injury would allow us to modulate the way in which adult tissue responds to injury. In this study, we employed secretome proteomics to compare fetal and adult protein regulation in response to cartilage injury using an ovine cartilage defect model. The most relevant events comprised proteins associated with the immune response and inflammation, proteins specific for cartilage tissue and cartilage development, and proteins involved in cell growth and proliferation. Alarmins S100A8, S100A9 and S100A12 and coiled-coil domain containing 88A (CCDC88A), which are associated with inflammatory processes, were found to be significantly upregulated following injury in adult, but not in fetal animals. By contrast, cartilage-specific proteins like proteoglycan 4 were upregulated in response to injury only in fetal sheep postinjury. Our results demonstrate the power and relevance of the ovine fetal cartilage regeneration model presented here for the first time. The identification of previously unrecognized modulatory proteins that plausibly affect the healing process holds great promise for potential therapeutic interventions., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Surgical repair of rotator cuff tears presents a significant clinical challenge with high failure rates and inferior functional outcomes. Graft augmentation improves repair outcomes; however, currently available grafting materials have limitations. Although cell-seeded decellularized tendon slices may facilitate cell infiltration, promote tendon incorporation, and preserve original mechanical strength, the unique fibrocartilage zone is yet to be successfully reestablished. In this study, we investigated the biological and mechanical properties of an engineered tendon-fibrocartilage-bone composite (TFBC) with cyclic tension (3% strain; 0.2 Hz). Decellularized TFBCs seeded with bone marrow-derived mesenchymal stem cell (BMSCs) sheets and subjected to mechanical stimulation for up to 7 days were characterised by histology, immunohistochemistry, scanning electron microscopy, mechanical testing, and transcriptional regulation. The decellularized TFBC maintained native enthesis structure and properties. Mechanically stimulated TFBC-BMSC constructs displayed increased cell migration after 7 days of culture compared with static groups. The seeded cell sheet not only integrated well with tendon scaffold but also distributed homogeneously and aligned to the direction of stretch under dynamic culture. Developmental genes were regulated including scleraxis, which was significantly upregulated with mechanical stimulation. The Young's modulus of the cell-seeded constructs was significantly higher compared with the noncell-seeded controls. In conclusion, the results of this study reveal that the TFBC-BMSC composite provides an ideal multilayer construct for cell seeding and growth, with mechanical preconditioning further enhances cell penetration and differentiation. The BMSC cell sheet revitalised TFBC in conjunction with mechanical stimulation could serve as a novel and primed biological patch to improve rotator cuff repair., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: In the glenohumeral joint, the long head of biceps brachii (LHBB) is exposed to tension and compression loading. The short head of biceps brachii (SHBB) works only in tension. It is known that tendon under compression might develop fibrocartilaginous metaplasia that improves the resistance to compression but reduces the resistance to tension. This study evaluated the presence of cartilage in LHBB and SHBB samples, supporting its possible role in tendon tear., Methods: Between 2014 and 2016, 13 samples of LHBB and SHBB were collected during surgery for shoulder instability, glenohumeral arthritis, and massive rotator cuff tears. The samples were stained with hematoxylin and eosin, safranin-O, and Alcian blue (pH 1.0) for light microscopy. Immunohistochemistry was performed using anti-S100, anti-collagen I and II, and anti-tenascin-C antibodies., Results: Histochemistry: LHBB samples showed matrix disorganization, with clusters of chondrocyte surrounded by collagen fibers and glycosaminoglycans. Safranin-O showed evident metachromasia. SHBB samples did not show any matrix disorganization or cartilaginous metaplasia. Immunohistochemistry: In all LHBB samples, anti-S100 and anti-collagen II showed cartilage in proximity of the tendon tear. Tenascin C immunostained closely to the disorganized matrix areas. SHBB, however, showed no positive areas for S-100, anti-collagen II, or tenascin C., Conclusions: According to our results, we hypothesize that the repeated stimulation in compression may induce the formation of fibrous cartilage. However, to date its role in tendon pathology remains to be clearly defined., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Temporomandibular joint degenerative disease (TMJ-DD) is a chronic form of TMJ disorder that specifically afflicts people over the age of 40 and targets women at a higher rate than men. Prevalence of TMJ-DD in this population suggests that estrogen loss plays a role in the disease pathogenesis. Thus, the goal of the present study was to determine the role of estrogen on chondrogenesis and homeostasis via estrogen receptor alpha (ERα) during growth and maturity of the joint. Young and mature WT and ERαKO female mice were subjected to ovariectomy procedures and then given placebo or estradiol treatment. The effect of estrogen via ERα on fibrocartilage morphology, matrix production, and protease activity was assessed. In the young mice, estrogen via ERα promoted mandibular condylar fibrocartilage chondrogenesis partly by inhibiting the canonical Wnt signaling pathway through upregulation of sclerostin (Sost). In the mature mice, protease activity was partly inhibited with estrogen treatment via the upregulation and activity of protease inhibitor 15 (Pi15) and alpha-2-macroglobulin (A2m). The results from this work provide a mechanistic understanding of estradiol on TMJ growth and homeostasis and can be utilized for development of therapeutic targets to promote regeneration and inhibit degeneration of the mandibular condylar fibrocartilage.

Purpose: To evaluate clinical outcomes, demographics, and radiographic findings for patients whose hip arthroscopies involved amorphous calcification (AC) excision and to compare them with a control group with no AC and with the general population regarding diabetes mellitus and hypothyroidism., Methods: Patients who underwent primary hip arthroscopy involving surgical excision of AC deposit in the anterosuperior labralcapsular recess between October 2008 and July 2014 were reviewed. Demographics, radiographic findings, intraoperative findings, and procedures were reviewed. Minimum follow-up was 2 years and included visual analog scale for pain, patient satisfaction, and the following patient-reported outcome scores: modified Harris hip score, hip outcomes score sport-specific subscale, and nonarthritic hip score. These patients were matched (1:2 ratio) to patients who underwent hip arthroscopy with no AC using the following matching criteria: age at surgery ± 5 years, body mass index ± 5, gender, type of labral treatment, and type of capsular treatment., Results: We reviewed 12 cases in 11 female patients. Mean latest follow-up scores improved from 64.0 to 83.4 (P = .003) for modified Harris hip score, from 57.6 to 80.6 (P < .001) for nonarthritic hip score, from 35.4 to 62.7 (P = .021) for hip outcomes score sport-specific subscale, and from 6.4 to 2.8 (P = .016) for visual analog scale. The survivorship rate was 91.7%, with one hip converting to total hip arthroplasty. Mean patient satisfaction was 8.4 ± 2.3. Six hips of the 12 (50%) had clock face localization of the AC. They were all between 11 and 12 with a mean of 12:30. Postoperative radiographic findings showed no subsequent AC in all 12 hips. No complications or revisions were reported. There were no significant differences between the AC group and the control group., Conclusions: The treatment of AC as part of hip arthroscopy for labral tear and femoro-acetabular impingement is safe and has favorable and similar outcomes compared with a control group at minimum 2-year follow-up. Female gender may be a risk factor for the development of AC. There is no strong evidence that AC should be debrided., Level of Evidence: Level III, case control study., (Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The acetabular labrum of the hip (ALH) is recognized as a clinically important structure, but knowledge about the pathophysiology of this fibrocartilage is scarce. In this prospective study we determined the prevalence of ALH calcification in patients with end-stage osteoarthritis (OA) and analyzed the relationship of cartilage calcification (CC) with hip pain and clinical function. Cohort of 80 patients (70.2 ± 7.6years) with primary OA scheduled for total hip replacement. Harris Hip Score (HHS) was recorded preoperatively. Total ALH and femoral head (FH) were sampled intraoperatively. CC of the ALH and FH was analyzed by high-resolution digital contact radiography. Histological degeneration of the ALH (Krenn-Score) and FH (OARSI-Score) was determined. Multivariate linear regression model and partial correlation analyses were performed. The prevalence of cartilage calcification both in the ALH and FH was 100%, while the amount of CC in the ALH was 1.55 times higher than in the FH (p < 0.001). There was a significant inverse regression between the amount of calcification of both the ALH and the FH and preoperative HHS (β ALH  = -2.1, p = 0.04), (β FH  = -2.9, p = 0.005), but pain was influenced only by ALH calcification (β ALH  = -2.7, p = 0.008). Age-adjusted, there was a significant correlation between cartilage calcification and histological degeneration (ALH:r s  = 0.53, p < 0.001/FH: r s  = 0.30, p = 0.007). Fibrocartilage and articular cartilage calcification are inseparable pathological findings in end-stage osteoarthritis of the hip. Fibrocartilage calcification is associated with poor and painful hip function., Clinical Significance: ALH fibrocartilage appears to be particularly prone to calcification, which may explain higher pain levels in individuals with a high degree of ALH calcification independent of age and histological degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1248-1255, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Enthesopathy is a disorder of bone, tendon, or ligament insertion. It represents one-fourth of all tendon-ligament diseases and is one of the most difficult tendon-ligament disorders to treat. Despite its high prevalence, the exact pathogenesis of this condition remains unknown. Here, we show that TGF-β was activated in both a semi-Achilles tendon transection (SMTS) mouse model and in a dorsiflexion immobilization (DI) mouse model of enthesopathy. High concentrations of active TGF-β recruited mesenchymal stromal stem cells (MSCs) and led to excessive vessel formation, bone deterioration, and fibrocartilage calcification. Transgenic expression of active TGF-β1 in bone also induced enthesopathy with a phenotype similar to that observed in SMTS and DI mice. Systemic inhibition of TGF-β activity by injection of 1D11, a TGF-β-neutralizing antibody, but not a vehicle antibody, attenuated the excessive vessel formation and restored uncoupled bone remodeling in SMTS mice. 1D11-treated SMTS fibrocartilage had increased proteoglycan and decreased collagen X and matrix metalloproteinase 13 expression relative to control antibody treatment. Notably, inducible knockout of the TGF-β type II receptor in mouse MSCs preserved the bone microarchitecture and fibrocartilage composition after SMTS relative to the WT littermate controls. Thus, elevated levels of active TGF-β in the enthesis bone marrow induce the initial pathological changes of enthesopathy, indicating that TGF-β inhibition could be a potential therapeutic strategy.

Purpose: Histological architecture of normal acetabular labrum regarding free nerve endings (FNEs) and mechanoreceptors (MRs) has been satisfactorily described in the literature. However, the presence of FNEs and MRs in acetabular labrum of hip joint has been analyzed only once in patients with osteoarthritis (OA). Aim of this article is to report histological distribution pattern of FNEs and MRs in acetabular labrum of patients with severe OA, at the same time conducting a comparison with normal acetabular labrum described in the literature., Methods: Seven patients with severe hip OA were enrolled in this study. Patient selection was assisted by the utilization of specific clinical scales delineated by the American College of Rheumatology. After successful total hip arthroplasty, tissue samples of acetabular labra of seven patients were histologically processed and stained with the gold standard chloride method, which was subsequently examined under a compound microscope., Results: FNEs and MRs constituted the major histological structures. Identified MRs included Pacini corpuscles, Ruffini corpuscles, and Golgi-Mazzoni corpuscles. The presence of FNEs was predominant in the middle part of the acetabular labrum, featuring a remarkable decrease in peripheral parts. In contrast, MRs were detected basically in peripheral parts and less in the middle part., Conclusions: Differentiation of the distribution pattern of MRs and FNEs in acetabular labrum of hip joint is remarkable between normal patients and patients with severe OA. The abundance of FNEs in the middle part of the pathologic labrum is mainly responsible for the observed discrimination. A "conversion" of MRs to FNEs may occur during OA progression, modulating therefore this pattern as well as the upcoming clinical manifestations.

Purpose: The purpose of this study was to determine whether or not there is a distinct pattern of injury to the acetabular labrum and/or cartilage in the hip with instability without bony dysplasia., Methods: Surgical records and intra-operative images of consecutive patients who underwent primary hip arthroscopy for femoroacetabular impingement (FAI) and/or hip instability by the senior author from April 2007 to December 2014 were retrospectively reviewed. Pathological changes were documented and charted on a novel diagram of the acetabulum, and classified into eight patterns corresponding to the lesion's location and size. In patients who had acetabular chondroplasty treatment, the width of the cartilage lesion was recorded., Results: A total of 953 hips in 886 patients were included, and patients who met our inclusion/exclusion criterion were grouped into an Instability-Only group (45 hips), an Instability-Dysplasia group (12 hips), as well as Pincer-FAI, Cam-FAI, and Combined-FAI groups consisting of 100, 54, and 269 hips, respectively. In the Instability-Only group, 42.2 % of the chondral and labral lesions demonstrated a "Straight-Anterior" pattern, which proportion was statistically significantly different compared with Pincer-FAI (p < 0.000), Cam-FAI (p = 0.0002), and Combined-FAI (p < 0.000) groups. In Instability-Only patients, only 15.6 % of the lesions had an "Anterior to Lateral" pattern, a significantly lower proportion (p < 0.000) compared with the FAI groups. Also 11.1 % of the lesions demonstrated a "Lateral" pattern, which is a significantly greater proportion compared with Pincer-FAI (p < 0.000) and Combined-FAI (p < 0.000) groups. The mean width of the cartilage lesions for the Instability-Only group was 2.9 mm, which was significantly shallower than for the other FAI groups (p < 0.000)., Conclusion: A significant predilection of "Straight-Anterior" or "Lateral" location of labral and/or cartilage damage was observed in the hip with instability, while there was shallow width of articular cartilage damage in these patients. These results suggest that there is a distinctive labral and cartilage damage pattern for hips with instability without inherent bony dysplasia., Level of Evidence: Diagnostic study, Level IV.

Fracture healing is a complex biological process involving the proliferation of mesenchymal progenitor cells, and chondrogenic, osteogenic, and angiogenic differentiation. The mechanisms underlying the proliferation and differentiation of mesenchymal progenitor cells remain unclear. Here, we demonstrate Dickkopf-related protein 3 (Dkk3) expression in periosteal cells using Dkk3-green fluorescent protein reporter mice. We found that proliferation of mesenchymal progenitor cells began in the periosteum, involving Dkk3-positive cell proliferation near the fracture site. In addition, Dkk3 was expressed in fibrocartilage cells together with smooth muscle α-actin and Col3.6 in the early phase of fracture healing as a cell marker of fibrocartilage cells. Dkk3 was not expressed in mature chondrogenic cells or osteogenic cells. Transient expression of Dkk3 disappeared in the late phase of fracture healing, except in the superficial periosteal area of fracture callus. The Dkk3 expression pattern differed in newly formed type IV collagen positive blood vessels and the related avascular tissue. This is the first report that shows Dkk3 expression in the periosteum at a resting state and in fibrocartilage cells during the fracture healing process, which was associated with smooth muscle α-actin and Col3.6 expression in mesenchymal progenitor cells. These fluorescent mesenchymal lineage cells may be useful for future studies to better understand fracture healing.

Objective: Using magnetic resonance imaging (MRI) to evaluate the characteristics of pathological changes of fibro-cartilage of the knee in patients with Baker cyst, to assess the compliance of degrees of damage stages of osteoarthritis on a scale of Kellgren–Lawrence (K–L), and compare the results with the data of other researchers., Material and Methods: This study included patients (38–82 years) with a cyst Baker accidentally detected during ultrasound veins of the lower extremities. The subjects underwent a single knee MRI. MRI was made in three dimensions using 3D gradient-echo protocol. Independent radiologist evaluated the presence and severity of chondral defect osteophytosis, damage to the menisci and ligaments, intraosseous edema and subchondral cysts. The osteoarthritis stage of the knee were identified by X-ray performed in a standing position in the standard two projections, with K–L scale., Results: In this study, the results of a survey of 20 people, whose average age was 57.2 years. According to the radiological scale of K–L two patients were assigned to the stage 0 degree, 5 people to stage 1, 2, 4 each, and 3 – to stage 3. Synovitis of various severity was detected in 85% of the studies. Nineteen visualized the patellar cartilage damage, the condyles of the femur and tibia are most commonly affects the joint area. Among the most commonly injured ligament anterior cruciate ligament was determined – 9 (45%) patients in the same amount of detected intramedullary edema condyles femur and tibia. Eighteen subjects had at least one anomaly meniscus detectable by MRI, while in 11 (55%) persons were deviations, at least two or more regions of the knee examined., Conclusions: Our results suggest that not all visualized on MRI degenerative damage to intra fibro-cartilaginous tissue correlate positively with the stages of osteoarthritis of the knee, identified by standard radiographs and may not significantly affect the onset and progression of synovial cyst of the popliteal region.

Background: Cartilage grafts are commonly used in nasal surgery for structural and/or esthetic purposes. The viability of cartilage grafts has been investigated in many forms since the use of cartilage grafts in surgical procedures., Objectives: The objective of this study was to investigate the viability of minced cartilage grafts and whether there is a difference between grafts wrapped in Surgicel(®) Original and Surgicel Fibrillar., Methods: A total of ten New Zealand rabbits were used for the study. Cartilage grafts were harvested from one side ear. Four groups were formed. Group 1: minced cartilage graft wrapped in Surgicel Fibrillar; Group 2: minced cartilage graft wrapped in Surgicel Original; Group 3: bare minced cartilage graft; and Group 4: bare diced cartilage graft. Four small subcutaneous pockets were made in the backs of the rabbits, and the grafts were placed in these pockets. All of the rabbits were sacrificed at the end of 3 months, and the samples were collected. The sections were stained with hematoxylin and eosin (H&E), toluidin blue, safranin-O, masson trichrome, and glial fibrillary acidic protein immunohistochemical. All specimens were assessed histopathologically under a light microscope., Results: There was no statistically significant difference between the Surgicel Fibrillar and Surgicel Original groups with respect to any of the parameters. Bone formation, calcification, inflammation, fibrosis, and basophilia were similar in all groups, with no significant difference among them. In the Surgicel Fibrillar and Surgicel Original groups, a heavy chondrocyte nucleus loss accompanied by a minimal peripheral proliferation was observed., Conclusions: The viability of bare minced cartilage grafts was found to be similar to that of bare diced cartilage in this study. Minced cartilage grafts can be used in the correction of minor dorsal defects and irregularities in persons with thin nasal skins, especially in primary and revision rhinoplasty. Although there is no statistically significant difference between the Surgicel Fibrillary and Surgicel Original groups, we think that, if it is necessary to use oxidized regenerated cellulose, it should be in the fibrillar form., No Level Assigned: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Interference screw in the fixation of autologous tendon graft to the bone tunnel is widely accepted for the reconstruction of anterior cruciate ligament (ACL), but the regeneration of fibrocartilaginous entheses could hardly be achieved with the traditional interference screw. In the present work, biodegradable high-purity magnesium (HP Mg) showed good cytocompatibility and promoted the expression of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), fibrocartilage markers (Aggrecan, COL2A1 and SOX-9), and glycosaminoglycan (GAG) production in vitro. The HP Mg screw was applied to fix the semitendinosus autograft to the femoral tunnel in a rabbit model of ACL reconstruction with titanium (Ti) screw as the control. The femur-tendon graft-tibia complex was retrieved at 3, 6, 9 and 12 weeks. Gross observation and range of motion (ROM) of the animal model reached normal levels at 12 weeks. No sign of host reaction was found in the X-ray scanning. The HP Mg group was comparable to the Ti group with respect to biomechanical properties of the reconstructed ACL, and the ultimate load to failure and stiffness increased 12 weeks after surgery. In the histological analysis, the HP Mg group formed distinct fibrocartilage transition zones at the tendon-bone interface 12 weeks after surgery, whereas a disorganized fibrocartilage layer was found in the Ti group. In the immunohistochemical analysis, highly positive staining of BMP-2, VEGF and the specific receptor for BMP-2 (BMPR1A) was shown at the tendon-bone interface of the HP Mg group compared with the Ti group. Furthermore, the HP Mg group had significantly higher expression of BMP-2 and VEGF than the Ti group in the early phase of tendon-bone healing, followed by enhanced expression of fibrocartilage markers and GAG production. Therefore we proposed that the stimulation of BMP-2 and VEGF by Mg ions was responsible for the fibrochondrogenesis of Mg materials. HP Mg was promising as a biodegradable interference screw with the potential to promote fibrocartilaginous entheses regeneration in ACL reconstruction., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The phenomenon of cartilage rim loading in defects exceeding the threshold diameter of 10 mm is well documented. Contoured defect fill off-loads the perimeter and counteracts further delamination and progression of defects. When biological procedures have failed, inlay arthroplasty follows these concepts. The human biological response to contoured metallic surface implants has not been described. Four patients underwent non-implant-related, second-look arthroscopy following inlay arthroplasty for bi- (n=3) and tricompartmental (n=1) knee arthrosis without subchondral bone collapse. Arthroscopic probing of the implant-cartilage interface of nine prosthetic components did not show signs of implant-cartilage gap formation, loosening, or subsidence. The implant periphery was consistently covered by cartilage confluence leading to a reduction of the original defect size diameter. Femoral condyle cartilage flow appeared to have more hyaline characteristics. Trochlear cartilage flow showed greater histological variability and less organization with fibrocartilage and synovialized scar tissue. This review reconfirmed previous basic science results and demonstrated effective defect fill and rim off-loading with inlay arthroplasty.

The posterior glenoid labrum has numerous surrounding structures and any of them can undergo derangement. It is prudent to consider the posterior glenoid labrum complex (PGLC) as a whole rather than simply the labral tissue in isolation when evaluating magnetic resonance imaging (MRI) of the shoulder. The PGLC contains the posterior capsulolabral junction, posterior capsule (posteroinferiorly , the posterior band of the inferior glenohumeral ligament), posterior chondro-osseous junction, posterior chondrolabral junction, posterior glenoid bone, posterior glenoid subchondral bone, posterior glenoid cartilage, posterior labrum, synovial fold (variably seen), and posterior glenoid periosteum (or periosteal sleeve). Noninvasive MRI techniques are the mainstay in evaluating PGLC injury with or without the use of intra-articular gadolinium contrast agents. When using the PGLC model, a spectrum of pathology can be stratified.

Objectives: The generation of transgenic mice expressing green fluorescent proteins (GFPs) has greatly aided our understanding of the development of connective tissues such as bone and cartilage. Perturbation of a biological system such as the temporomandibular joint (TMJ) within its adaptive remodeling capacity is particularly useful in analyzing cellular lineage progression. The objectives of this study were to determine: (i) if GFP reporters expressed in the TMJ indicate the different stages of cell maturation in fibrocartilage and (ii) how mechanical loading affects cellular response in different regions of the cartilage., Design/methods: Four-week-old transgenic mice harboring combinations of fluorescent reporters (Dkk3-eGFP, Col1a1(3.6 kb)-GFPcyan, Col1a1(3.6 kb)-GFPtpz, Col2a1-GFPcyan, and Col10a1-RFPcherry) were used to analyze the expression pattern of transgenes in the mandibular condylar cartilage (MCC). To study the effect of TMJ loading, animals were subjected to forced mouth opening with custom springs exerting 50 g force for 1 h/day for 5 days. Dynamic mineralization and cellular proliferation (EdU-labeling) were assessed in loaded vs control mice., Results: Dkk3 expression was seen in the superficial zone of the MCC, followed by Col1 in the cartilage zone, Col2 in the prehypertrophic zone, and Col10 in the hypertrophic zone at and below the tidemark. TMJ loading increased expression of the GFP reporters and EdU-labeling of cells in the cartilage, resulting in a thickness increase of all layers of the cartilage. In addition, mineral apposition increased resulting in Col10 expression by unmineralized cells above the tidemark., Conclusion: The TMJ responded to static loading by forming thicker cartilage through adaptive remodeling., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

The femoral enthesis of the human anterior cruciate ligament (ACL) is known to be more susceptible to injury than the tibial enthesis. To determine whether anatomic differences might help explain this difference, we quantified the microscopic appearance of both entheses in 15 unembalmed knee specimens using light microscopy, toluidine blue stain and image analysis. The amount of calcified fibrocartilage and uncalcified fibrocartilage, and the ligament entheseal attachment angle were then compared between the femoral and tibial entheses via linear mixed-effects models. The results showed marked differences in anatomy between the two entheses. The femoral enthesis exhibited a 3.9-fold more acute ligament attachment angle than the tibial enthesis (p<0.001), a 43% greater calcified fibrocartilage tissue area (p<0.001), and a 226% greater uncalcified fibrocartilage depth (p<0.001), with the latter differences being particularly pronounced in the central region. We conclude that the ACL femoral enthesis has more fibrocartilage and a more acute ligament attachment angle than the tibial enthesis, which provides insight into why it is more vulnerable to failure., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Current cartilage repair histological scoring systems are unable to explain the relationship between collagen type II deposition and overall repair quality., Purpose/hypothesis: The purpose of this study was to develop a novel zonal collagen type (ZCT) 5-point scoring system to measure chondroinduction in human clinical biopsy specimens collected after marrow stimulation. The hypothesis was that the ZCT scores would correlate with the International Cartilage Repair Society-II (ICRS-II) overall histological repair assessment score and glycosaminoglycan (GAG) content., Study Design: Descriptive laboratory study., Methods: After optimizing safranin O staining for GAG and immunostaining for human collagen type II and type I (Col2 and Col1, respectively), serial sections from clinical osteochondral repair biopsy specimens (13 months after microfracture or microfracture with BST-CarGel; n = 39 patients) were stained and 3 blinded readers performed histomorphometry for percentage of staining, ICRS-II histological scoring, polarized light microscopy (PLM) scoring, and 5-point ZCT scoring based on tidemark morphology, zonal distribution of Col2 and Col1, and Col1 percentage stain. Because 1 biopsy specimen was missing bone, 38 biopsy specimens were evaluated for ICRS-II, PLM, and ZCT scores., Results: Chondroinduction was identified in 21 biopsy specimens as a Col2 matrix fused to bone that spanned the deep-middle-superficial zones ("full-thickness hyaline repair"), deep-middle zones, or deep zone ("stalled hyaline") that was covered with a variable-thickness Col1-positive matrix, and was scored, respectively, as ZCT = 1 (n = 4 biopsy specimens), ZCT = 2 (n = 6) and ZCT = 3 (n = 11). Other biopsy specimens (n = 17) were fibrocartilage (n = 9; ZCT = 4), fibrous tissue (n = 4, ZCT = 5), or non-marrow derived (n = 4; ZCT = 0). Non-marrow derived tissue had a mean mature tidemark score of 84 out of 100 versus a regenerating tidemark score of 24 for all other biopsy specimens (P = .005). Both "stalled hyaline" repair and fibrocartilage had the same mean Col2 percentage stain; however, fibrocartilage was distinguished by heavy Col1 deposits in the deep zone, a 2-fold higher mean Col1 percentage stain (P = .001), and lower surface integrity (P = .03). ZCT scores correlated with GAG content and the ICRS-II overall assessment score, especially when combined with the PLM score for collagen organization (R = 0.82). Histological scores of the deep zone strongly predicted the ICRS-II overall assessment score (R = 0.99)., Conclusion: The ICRS-II overall repair assessment score and GAG content correlated with the extent of Col2 deposition free of fibrosis in the deep/middle zone rather than bulk accumulation of Col2., Clinical Relevance: Biopsy tissue from the BST-CarGel randomized clinical trial (microfracture without and with BST-CarGel, as treatment groups were not unblinded) showed regenerated tissue consistent with a chondroinduction mechanism in at least half of the treated lesions., (© 2015 The Author(s).)

Temporomandibular joint ankylosis (TMJA) is a severe organic disease with progressive limitation of the mouth opening. Histopathologically, a residual joint space is reported to consist of fibrous tissue and/or cartilage, indicating two types of interface (osteo-fibrous and osteo-chondral) of residual joint space. It is well known that adverse mechanical stress results in pathological changes of osteoarthritis and enthesopathy in these interfaces. What would happen pathologically in these interfaces of TMJA under repeated mandible movement has not been elucidated. Fourteen tissue samples of residual joint space and temporal and condylar bone were stained with hematoxylin and eosin and evaluated by collagen I and II immunohistochemistry. A pathological study of 14 TMJA patients showed that the residual joint space presented a fibrocartilage entheses structure and an articular cartilage structure. Moreover, these two structures were associated with pathological alterations of both osteoarthritis and enthesopathy, including degenerated and necrotized tissue, chondrocyte cloning, crack and fissure, various bone scleroses, and inflammatory granulation tissue. It is suggested that the pathological alterations of both osteoarthritis and enthesopathy occurred in TMJA, which hints at mechanical stress on TMJA development., (Copyright © 2015. Published by Elsevier Ltd.)

Objective: A major challenge to understanding osteoarthritis (OA) pathology is identifying the cellular events that precede the onset of cartilage damage. The objective of this study is to determine the effect of joint destabilization on early changes to fibrocartilage in the joint., Design/methods: The anterior cruciate ligament was transected in collagen reporter mice (Col1CFP and ColXRFP). Mineralization labels were given every 2 weeks to measure new mineralized cartilage apposition. Novel fluorescent histology of mineralized tissue was used to characterize the changes in fibrocartilage at 2 and 4 weeks post-injury., Results: Changes in fibrocartilaginous structures of the joint occur as early as 2 weeks after injury and are well developed by 4 weeks. The alterations are seen in multiple entheses and in the medial surface of the femoral and tibial condyles. In the responding entheses, mineral apposition towards the ligament midsubstance results in thickening of the mineralize fibrocartilage. These changes are associated with increases in ColX-RFP, Col1-CFP reporter activity and alkaline phosphatase enzyme activity. Mineral apposition also occurs in the fibrocartilage of the non-articular regions of the medial condyles by 2 weeks and develops into osteophytes by 4 weeks post-injury. An unexpected observation is punctate expression of tartrate resistant acid phosphatase activity in unmineralized fibrochondrocytes adjacent to active appositional mineralization., Discussion: These observations suggest that fibrocartilage activates prior to degradation of the articular cartilage. Thus clinical and histological imaging of fibrocartilage may be an earlier indicator of disease initiation and may indicate a more appropriate time to start preventative treatment., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to describe the anatomy as seen arthroscopically, the role of the labrum and its relevance in luxation and reduction procedures, and secondary changes to the cartilaginous acetabular roof and to determine the main obstacles preventing reduction of dislocated hips in infants and young children., Methods: A specialized pediatric medial approach to hip arthroscopy was performed on 25 hip joints in 21 patients younger than 4 years of age. The arthroscopic procedure was conducted using a 2.7-mm cannulated instrument. A subadductor portal was used for the 70° arthroscope, and a high anterolateral portal served as a working portal. The anatomic findings of the individual hip joints were recorded. We examined the femoral head, the teres ligament, the transverse ligament, the acetabulum, and the acetabular labrum. The obstacles preventing reduction were successively resected., Results: An arthroscopic investigation of all major structures and arthroscopic reduction was possible in 25 hip joints. A hypertrophic teres ligament was present in 23 of the 25 hips. Capsular constriction prevented reduction in 22 of the 25 hips. The acetabular labrum was not inverted in any of the examined hip joints and was also never an obstacle to reduction. Secondary changes to the cartilaginous preformed acetabular roof were present in 10 hips., Conclusions: We have shown that arthroscopy of a developmentally dislocated hip can be safely performed using the subadductor portal. Through this arthroscopic approach, we were able to identify the previously described pathologic structures-the limbus, neolimbus, pulvinar, hypertrophic teres ligament, and capsular constriction. The capsule was the most common block to reduction, followed by the teres ligament. Successful reduction can be achieved by removal of intra-articular tissues, the pulvinar, and the teres ligament, and nearly always a capsular release. The limbus and neolimbus were not factors in achieving reduction in our series., Level of Evidence: Level IV, case series., (Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: There are limited clinical treatments for temporomandibular joint (TMJ) pathologies, including degenerative disease, disc perforation and heterotopic ossification (HO). One barrier hindering the development of new therapies is that animal models recapitulating TMJ diseases are poorly established. The objective of this study was to develop an animal model for TMJ cartilage degeneration and disc pathology, including disc perforation and soft tissue HO., Methods: New Zealand white rabbits (n = 9 rabbits) underwent unilateral TMJ disc perforation surgery and sham surgery on the contralateral side. A 2.5 mm defect was created using a punch biopsy in rabbit TMJ disc. The TMJ condyles and discs were evaluated macroscopically and histologically after 4, 8 and 12 weeks. Condyles were blindly scored by four independent observers using OARSI recommendations for macroscopic and histopathological scoring of osteoarthritis (OA) in rabbit tissues., Results: Histological evidence of TMJ condylar cartilage degeneration was apparent in experimental condyles following disc perforation relative to sham controls after 4 and 8 weeks, including surface fissures and loss of Safranin O staining. At 12 weeks, OARSI scores indicated experimental condylar cartilage erosion into the subchondral bone. Most strikingly, HO occurred within the TMJ disc upon perforation injury in six rabbits after 8 and 12 weeks., Conclusion: We report for the first time a rabbit TMJ injury model that demonstrates condylar cartilage degeneration and disc ossification, which is indispensible for testing the efficacy of potential TMJ therapies., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Integration of engineered musculoskeletal tissues with adjacent native tissues presents a significant challenge to the field. Specifically, the avascularity and low cellularity of cartilage elicit the need for additional efforts in improving integration of neocartilage within native cartilage. Self-assembled neocartilage holds significant potential in replacing degenerated cartilage, though its stabilization and integration in native cartilage require further efforts. Physical and enzymatic stabilization methods were investigated in an in vitro model for temporomandibular joint (TMJ) disc degeneration. First, in phase 1, suture, glue and press-fit constructs were compared in TMJ disc intermediate zone defects. In phase 1, suturing enhanced interfacial shear stiffness and strength immediately; after four weeks, a 15-fold increase in stiffness and a ninefold increase in strength persisted over press-fit. Neither suture nor glue significantly altered neocartilage properties. In phase 2, the effects of the enzymatic stabilization regimen composed of lysyl oxidase, CuSO4 and hydroxylysine were investigated. A full factorial design was employed, carrying forward the best physical method from phase 1, suturing. Enzymatic stabilization significantly increased interfacial shear stiffness after eight weeks. Combined enzymatic stabilization and suturing led to a fourfold increase in shear stiffness and threefold increase in strength over press-fit. Histological analysis confirmed the presence of a collagen-rich interface. Enzymatic treatment additionally enhanced neocartilage mechanical properties, yielding a tensile modulus over 6 MPa and compressive instantaneous modulus over 1200 kPa at eight weeks. Suturing enhances stabilization of neocartilage, and enzymatic treatment enhances functional properties and integration of neocartilage in the TMJ disc. Methods developed here are applicable to other orthopaedic soft tissues, including knee meniscus and hyaline articular cartilage., (© 2014 The Author(s) Published by the Royal Society. All rights reserved.)

Purpose: The purpose of this study was to define the limits of diagnostic glenohumeral arthroscopy and determine the prevalence and frequency of hidden extra-articular "bicipital tunnel" lesions among chronically symptomatic patients., Methods: Eight fresh-frozen cadaveric specimens underwent diagnostic glenohumeral arthroscopy with percutaneous tagging of the long head of the biceps tendon (LHBT) during maximal tendon excursion. The percentage of visualized LHBT was calculated relative to the distal margin of subscapularis tendon and the proximal margin of the pectoralis major tendon. Then, a retrospective review of 277 patients who underwent subdeltoid transfer of the LHBT to the conjoint tendon were retrospectively analyzed for lesions of the biceps-labral complex. Lesions were categorized by anatomic location (inside, junctional, or bicipital tunnel). Inside lesions were labral tears. Junctional lesions were LHBT tears visualized during glenohumeral arthroscopy. Bicipital tunnel lesions were extra-articular lesions hidden from view during standard glenohumeral arthroscopy., Results: Seventy-eight percent of LHBT were visualized relative to the distal margin of the subscapularis tendon and only 55% relative to the proximal margin of the pectoralis major tendon. No portion of the LHBT inferior to the subscapularis tendon was visualized. Forty-seven percent of patients had hidden bicipital tunnel lesions. Scarring was most common and accounted for 48% of all such lesions. Thirty-seven percent of patients had multiple lesion locations. Forty-five percent of patients with junctional lesions also had hidden bicipital tunnel lesions. The only offending lesion was in the bicipital tunnel for 18% of patients., Conclusions: Diagnostic glenohumeral arthroscopy fails to fully evaluate the biceps-labral complex because it visualizes only 55% of the LHBT relative to the proximal margin of the pectoralis major tendon and did not identify extra-articular bicipital tunnel lesions present in 47% of chronically symptomatic patients., Level of Evidence: Level IV, therapeutic case series and cadaveric study., (Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Sclerostin deficiency, via genetic knockout or anti-Sclerostin antibody treatment, has been shown to cause increased bone volume, density and strength of calluses following endochondral bone healing. However, there is limited data on the effect of Sclerostin deficiency on the formative early stage of fibrocartilage (non-bony tissue) formation and removal. In this study we extensively investigate the early fibrocartilage callus. Closed tibial fractures were performed on Sost(-/-) mice and age-matched wild type (C57Bl/6J) controls and assessed at multiple early time points (7, 10 and 14days), as well as at 28days post-fracture after bony union. External fixation was utilized, avoiding internal pinning and minimizing differences in stability stiffness, a variable that has confounded previous research in this area. Normal endochondral ossification progressed in wild type and Sost(-/-) mice with equivalent volumes of fibrocartilage formed at early day 7 and day 10 time points, and bony union in both genotypes by day 28. There were no significant differences in rate of bony union; however there were significant increases in fibrocartilage removal from the Sost(-/-) fracture calluses at day 14 suggesting earlier progression of endochondral healing. Earlier bone formation was seen in Sost(-/-) calluses over wild type with greater bone volume at day 10 (221%, p<0.01). The resultant Sost(-/-) united bony calluses at day 28 had increased bone volume fraction compared to wild type calluses (24%, p<0.05), and the strength of the fractured Sost(-/-) tibiae was greater than that that of wild type fractured tibiae. In summary, bony union was not altered by Sclerostin deficiency in externally-fixed closed tibial fractures, but fibrocartilage removal was enhanced and the resultant united bony calluses had increased bone fraction and increased strength., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

Expanded costochondral cells provide a clinically relevant cell source for engineering both fibrous and hyaline articular cartilage. Expanding chondrocytes in a monolayer results in a shift toward a proliferative, fibroblastic phenotype. Three-dimensional aggregate culture may, however, be used to recover chondrogenic matrix production. This study sought to engineer a spectrum of fibrous to hyaline neocartilage from a single cell source by varying the duration of three-dimensional culture following expansion. In third passage porcine costochondral cells, the effects of aggregate culture duration were assessed after 0, 8, 11, 14, and 21 days of aggregate culture and after 4 subsequent weeks of neocartilage formation. Varying the duration of aggregate redifferentiation generated a spectrum of fibrous to hyaline neocartilage. Within 8 days of aggregation, proliferation ceased, and collagen and glycosaminoglycan production increased, compared with monolayer cells. In self-assembled neocartilage, type II-to-I collagen ratio increased with increasing aggregate duration, yet glycosaminoglycan content varied minimally. Notably, 14 days of aggregate redifferentiation increased collagen content by 25%, tensile modulus by over 110%, and compressive moduli by over 50%, compared with tissue formed in the absence of redifferentiation. A spectrum of fibrous to hyaline cartilage was generated using a single, clinically relevant cell source, improving the translational potential of engineered cartilage.

Objective: Assess the diagnostic accuracy of 3-T indirect magnetic resonance arthrography (iMRA) for hip cartilage and labral pathology detection using arthroscopy as the reference standard and compare it to the published performance of direct magnetic resonance arthrography (dMRA)., Materials and Methods: Between 2009 and 2011, 290 patients suspected of having femoroacetabular impingement underwent iMRA. Our study group consisted of 41 of these patients (17 males, mean age 35 years; 24 females, mean age 33 years) who did not have a prior history of hip surgery and who subsequently underwent arthroscopy. Two experienced musculoskeletal radiologists separately evaluated the randomized and anonymized studies for the presence and quadrant location of labral and cartilage pathology. These recorded data were compared to arthroscopic reports., Results: Forty-one patients had labral pathology, 34 patients had acetabular and 5 patients had femoral cartilage pathology at arthroscopy. Sensitivity, specificity, accuracy, negative- and positive-predictive values for labral lesion detection were respectively 98, 99, 99, 99 and 98 %; for acetabular cartilage lesion detection they were 69, 98, 89, 87 and 95 %; for femoral cartilage lesion detection they were 69, 95, 93 and 39 %. Sensitivities of iMRA by quadrant (anteroinferior, anterosuperior, posteroinferior, posterosuperior) for the labrum were 100.0, 95.0, NA and 85.7 %, for acetabular cartilage were NA, 58.8, NA and 39.5 % and for femoral cartilage were 50.0, 33.3, 75.0 and 75.0 %). NA indicates results not available because of the absence of findings in those quadrants. Specificities of iMRA by quadrant (anteroinferior, anterosuperior, posteroinferior, posterosuperior) for the labrum (95.0, 100.0, 95.1, 67.5 %), acetabular (100.0, 85.7, 92.6, 79.5 %) and femoral cartilage (100.0, 94.7, 96.2, 85.9 %)., Conclusion: iMRA at 3 T is accurate in detecting labral pathology suggesting that it is a viable alternative to dMRA.

Objective: To 1) test the feasibility of delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) at 3 T in the temporomandibular joint (TMJ) and 2) to determine the optimal delay for measurements of the TMJ disc after i.v. contrast agent (CA) administration., Design: MRI of the right and left TMJ of six asymptomatic volunteers was performed at 3 T using a dedicated coil. 2D inversion recovery (2D-IR) sequences were performed at 4 time points covering 120 minutes and 3D gradient-echo (3D GRE) dual flip-angle sequences were performed at 14 time points covering 130 minutes after the administration of 0.2 mmol/kg of Gd-diethylenetriamine pentaacetic acid ion (Gd-DTPA)(2-), i.e., 0.4 mL of Magnevist™ per kg body weight. Pair-wise tests were used to assess differences between pre-and post-contrast T1 values., Results: 2D-IR sequences showed a statistically significant drop (p<0.001) in T1 values after i.v. CA administration. The T1 drop of 50% was reached 60 minutes after bolus injection in the TMJ disc. The 3D GRE dual flip-angle sequences confirmed these results and show plateau of T1 after 60 minutes., Conclusions: T1(Gd) maps calculated from dGEMRIC data allow in vivo assessment of the fibrocartilage disc of the TMJ. The recommended measurement time for dGEMRIC in the TMJ after i.v. CA administration is from 60 to 120 minutes., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

The pathophysiology of rapidly destructive osteoarthritis (OA) of the hip is unknown. This study documented cases of inversion of the acetabular labrum, which has clinicoradiologic features similar to those of initial-stage rapidly destructive hip OA. Our study was based on a prospective review of data for 9 patients with rapidly destructive hip OA. Intraoperative findings showed that the anterosuperior portion of the acetabular labrum had inverted into the articular space, along with many fragments of articular cartilage, in all patients. Subchondral insufficiency fractures of the femoral heads were seen just under the inverted labra in 8 of the 9 patients. Inversion of the acetabular labrum may be involved in rapid joint-space narrowing and subchondral insufficiency fracture in rapidly destructive hip OA., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration., Hypothesis: After the repair of a chronic rotator cuff tear in rats, licofelone would increase the load to failure of repaired tendons and increase the force production of muscle fibers., Study Design: Controlled laboratory study., Methods: Rats underwent supraspinatus release followed by repair 28 days later. After repair, rats began a treatment regimen of either licofelone or a vehicle for 14 days, at which time animals were euthanized. Supraspinatus muscles and tendons were then subjected to contractile, mechanical, histological, and biochemical analyses., Results: Compared with controls, licofelone-treated rats had a grossly apparent decrease in inflammation and increased fibrocartilage formation at the enthesis, along with a 62% increase in the maximum load to failure and a 51% increase in peak stress to failure. Licofelone resulted in a marked reduction in fibrosis and lipid content in supraspinatus muscles as well as reduced expression of several genes involved in fatty infiltration. Despite the decline in fibrosis and fat accumulation, muscle fiber specific force production was reduced by 23%., Conclusion: The postoperative treatment of cuff repair with licofelone may reduce fatty degeneration and enhance the development of a stable bone-tendon interface, although decreases in muscle fiber specific force production were observed, and force production in fact declined., Clinical Relevance: This study demonstrates that the inhibition of 5-LOX, COX-1, and COX-2 modulates the healing process of repaired rotator cuff tendons. Although further studies are necessary, the treatment of patients with licofelone after cuff repair may improve the development of a stable enthesis and enhance postoperative outcomes., (© 2014 The Author(s).)

Background: Recent studies suggest that fluoroquinolone antibiotics predispose tendons to tendinopathy and/or rupture. However, no investigations on the reparative capacity of tendons exposed to fluoroquinolones have been conducted., Hypothesis: Fluoroquinolone-treated animals will have inferior biochemical, histological, and biomechanical properties at the healing tendon-bone enthesis compared with controls., Study Design: Controlled laboratory study., Methods: Ninety-two rats underwent rotator cuff repair and were randomly assigned to 1 of 4 groups: (1) preoperative (Preop), whereby animals received fleroxacin for 1 week preoperatively; (2) pre- and postoperative (Pre/Postop), whereby animals received fleroxacin for 1 week preoperatively and for 2 weeks postoperatively; (3) postoperative (Postop), whereby animals received fleroxacin for 2 weeks postoperatively; and (4) control, whereby animals received vehicle for 1 week preoperatively and for 2 weeks postoperatively. Rats were euthanized at 2 weeks postoperatively for biochemical, histological, and biomechanical analysis. All data were expressed as mean ± standard error of the mean (SEM). Statistical comparisons were performed using either 1-way or 2-way ANOVA, with P < .05 considered significant., Results: Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) analysis revealed a 30-fold increase in expression of matrix metalloproteinase (MMP)-3, a 7-fold increase in MMP-13, and a 4-fold increase in tissue inhibitor of metalloproteinases (TIMP)-1 in the Pre/Postop group compared with the other groups. The appearance of the healing enthesis in all treated animals was qualitatively different than that in controls. The tendons were friable and atrophic. All 3 treated groups showed significantly less fibrocartilage and poorly organized collagen at the healing enthesis compared with control animals. There was a significant difference in the mode of failure, with treated animals demonstrating an intrasubstance failure of the supraspinatus tendon during testing. In contrast, only 1 of 10 control samples failed within the tendon substance. The healing enthesis of the Pre/Postop group displayed significantly reduced ultimate load to failure compared with the Preop, Postop, and control groups. There was no significant difference in load to failure in the Preop group compared with the Postop group. Pre/Postop animals demonstrated significantly reduced cross-sectional area compared with the Postop and control groups. There was also a significant reduction in area between the Preop and control groups., Conclusion: In this preliminary study, fluoroquinolone treatment negatively influenced tendon healing., Clinical Relevance: These findings indicate that there was an active but inadequate repair response that has potential clinical implications for patients who are exposed to fluoroquinolones before tendon repair surgery., (© 2014 The Author(s).)

This study was to investigate whether surgically created incisions in discs at different sizes would heal spontaneously. Thirty mature goats were randomly divided into group A (1 mm), group B (3 mm) and group C (5 mm) according to the length of incision on the discs. Five animals in each group were sacrificed at 3 and 6 months postoperatively. The disc and condyle were evaluated by gross, histological and immunohistochemistry examinations. 1-mm discal incisions healed spontaneously with nearly normal gross and histological appearance at 6 months postoperatively, while 3-mm and 5-mm discal incisions failed to heal. Degenerative changes were observed in the fibrocartilage in both 3-mm and 5-mm incision groups, with a greater extent in the 5-mm group. Our results suggested that the TMJ disc of goat has limited self-repair capability to damage, which will be useful for making pre-surgical decisions related to the size and healing period of TMJ disc perforations., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats., Methods: Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed., Results: When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment., Conclusion: It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Juvenile idiopathic arthritis (JIA) is an autoimmune, heterogeneous disease and the temporomandibular joint (TMJ) can be affected, with consequences for mandibular growth and function. The aim of this study was to evaluate the importance of longitudinal medical treatment and the burden of disease activity on the development of temporomandibular condylar alterations as judged on panoramic radiographs., Methods: The study was a retrospective evaluation of dental and medical records in consecutive JIA patients referred to three specialist dental clinics in Sweden during an eight-year period. Data on the total pharmacological treatment and disease activity were evaluated longitudinally from disease onset to the time of the panoramic examination, during a median observation period of 2.5 years. The radiographs were analysed in terms of structural and shape alterations in the condyles and judged dichotomously., Results: Panoramic examinations were analysed in 158 patients from 266 referrals diagnosed with JIA. Condylar alterations (shape or structural) were seen in 68 patients (43%). Patients with condylar alterations were more extensively treated over time compared with those without condylar alterations. Powerful disease activity and/or potent medication at any time during the course of the disease implied an increased risk of alterations., Conclusions: Patients with JIA who require more intensive medication over time run the greatest risk of condylar alterations. As yet, current medical programmes have not been specified for the TMJ and more knowledge in this area is needed.

Background: This study examined histologic characteristics and biomechanical performance of 2 commercially available, small glenoid anchors., Methods: Adult research dogs (n = 6) were used for histologic analysis. Anchors were inserted into the lateral rim of the glenoid using the manufacturer's protocol. The dogs were humanely euthanatized 8 weeks after anchor implantation, and the glenoids were collected for histologic analysis. Bone socket width data were compared for statistically significant (P < .05) differences. In addition, 4 matched pairs (n = 8) of human cadaveric glenoids were instrumented with 1 BioComposite SutureTak (Arthrex, Naples, FL, USA) and 1 JuggerKnot (Biomet, Warsaw, IN, USA) suture anchor in the anterior-inferior quadrant. Anchor constructs were preloaded to 5 N, cycled from 5 to 25 N for 100 cycles, and then pulled to failure., Results: All JuggerKnot anchor sites were cyst-like cavities with a rim of dense lamellar bone. All BioComposite SutureTak anchor sites contained intact anchors with close approximation of anastomosing trabeculae of lamellar bone. At 8 weeks after implantation, mean socket width of the JuggerKnot anchor sites was 6.3 ± 2.5 mm, which was significantly (P = .013) larger than the mean socket width of 2.7 ± 0.7 mm measured for the BioComposite SutureTak anchor sites. The JuggerKnot anchor demonstrated larger displacements during subfailure cyclic loading (2.9 ± 1.0 mm compared with 1.3 ± 0.4 mm) and load to failure tests (13.7 ± 6.6 mm compared with 3.2 ± 0.5 mm). Statistical differences (P < .01) existed in every category except ultimate load., Conclusions: Based on the biomechanical in human bone and histologic findings in canine subjects, the all-suture anchor may be at risk for clinical failure., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)