Search

BACKGROUND: Swimming is an important non-pharmacological treatment for knee osteoarthritis, which can effectively alleviate the disease. However, the effect and mechanism of swimming on senile knee osteoarthritis are still unclear. OBJECTIVE: To investigate the effect of swimming exercise on the articular cartilage of aged mice with knee osteoarthritis. METHODS: Six 3-month-old male C57BL/6 mice were selected as the young group, and twelve 18-month-old male C57BL/6 mice were randomized into the aged group and the swimming group, with six mice in each group. Mice in the swimming group received adaptive swimming for 1 week and formal swimming for 8 weeks. After the intervention, stride length analysis and sampling were performed in each group. The total number of leukocytes and lymphocytes in peripheral blood was detected by blood routine examinations. The morphology of the articular cartilage was observed by hematoxylin-eosin and safranin O-fast green staining. Chondrocyte counts and the modified Mankin’s score were used to evaluate the degree of articular cartilage damage. The protein and mRNA expressions of type II collagen, aggrecan and matrix metalloproteinase 13 in articular cartilage were detected by immunohistochemical staining and RT-qPCR. RESULTS AND CONCLUSION: Compared with the young group, the mice in the aged group showed significantly decreased stride length (P < 0.05), significantly increased numbers of peripheral leukocytes and lymphocytes (P < 0.05), significantly decreased count of chondrocytes (P < 0.05), significantly increased modified Mankin’s score (P < 0.05), significantly decreased protein and mRNA expression of type II collagen and aggreca (P < 0.05), and significantly increased matrix metalloproteinase 13 expression (P < 0.05). Moreover, hematoxylin-eosin and safranin O-fast green staining showed the uneven surface of the articular cartilage, abnormal chondrocytes, and proteoglycan loss in the aged group. Compared with the aged group, swimming exercise significantly improved the stride length of mice (P < 0.05), decreased the count of peripheral blood lymphocytes (P < 0.05), increased the count of chondrocytes (P < 0.05), decreased the modified Mankin’s score (P < 0.05), increased the protein and mRNA expression of type II collagen and aggrecan (P < 0.05), and decreased the expression of matrix metalloproteinase 13 (P < 0.05). Hematoxylin-eosin and safranin O-fast green staining showed that the articular surface of mice in the swimming group was smooth, chondrocytes were normal, and proteoglycan loss was less. All these findings indicate that swimming exercise can reduce the number of inflammatory cells in the blood of aged mice, improve articular chondrocytes, matrix composition and cartilage tissue morphology; thus, it has a protective effect on the cartilage of aged mice with knee osteoarthritis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Growth differentiation factor 5, a member of the transforming growth factor-β superfamily and bone morphogenetic protein family, plays an important role in articular cartilage injury repair, bone regeneration, improvement of intervertebral disc degeneration, tendon healing, and neurodevelopment. OBJECTIVE: To review the research progress of growth differentiation factor 5 in inducing chondrocytes, nucleus pulposus-like cells, tendon cell differentiation, as well as inducing bone formation and neurodevelopment. METHODS: The search terms “growth differentiation factor 5, articular cartilage, bone, nucleus pulposus cells, tendon, nerve regeneration” were used in CNKI, WanFang and PubMed. According to the inclusion and exclusion criteria, the articles not related to the subject matter were excluded and 69 articles related to growth differentiation factor 5 were included. RESULTS AND CONCLUSION: (1) Growth differentiation factor 5 can induce chondrogenic and osteoblastic differentiation of mesenchymal stem cells, but the concentration boundary of growth differentiation factor 5 to induce chondrogenic or osteoblastic differentiation remains unclear. (2) Growth differentiation factor 5 can induce mesenchymal stem cells to differentiate into nucleus pulposus cells, which may play a role in the treatment of intervertebral disc degeneration. (3) Growth differentiation factor 5 can induce mesenchymal stem cells to differentiate into tendon cells and play an important role in tendon repair and prevention of postoperative tendon adhesion. (4) Growth differentiation factor 5 can induce neurodevelopment and promote nerve regeneration. [ABSTRACT FROM AUTHOR]

Purpose of the Study: The evaluation of anti-apoptotic and chondroprotective properties of a single injection of PRP using immunohistochemistry (IHC). Methods: This was a placebo-controlled blinded experimental study. Ten healthy Dunkin Hartley guinea pigs were selected. One knee of each animal was injected with a single injection of PRP (Group A); the contralateral knee acted as a control and was injected with a single injection of normal saline (Group B). These groups were further divided into A3 and B3 based on the timeline of animal sacrifice (3 months) and A6 and B6 (6 months). The formalin-preserved articular cartilage blocks were subjected to IHC to stain Aggrecan, Caspase-3, and Collagen-2. Results: The mean IHC score was significantly low for Caspase-3 (p—0.029) in intervention group (A3) in comparison to placebo control group (B3) pointing towards decreased apoptosis. The mean IHC values were significantly higher for Collagen II (p—0.011) for intervention group (A6) in contrast to control group (B6); values were also significantly low for Caspase-3 (p—0.029) in A6 as compared to B6. The mean Caspase-3 values were significantly higher in A6 as compared to A3 (p—0.029). Conclusion: The impact of a solitary injection of PRP on upregulation of anabolic pathways inside cartilage is relatively slower as compared to its effect on downregulation of apoptotic pathways. Even a single PRP injection holds the potential to change cartilage microenvironment, but the effects are not long lasting. [ABSTRACT FROM AUTHOR]

Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements that contain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care. Joint lubrication is important for minimizing friction between articulating joint surfaces and for preventing cartilage wear that can otherwise exacerbate osteoarthritis. This Review examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. Key points: In osteoarthritis, compositional changes to the synovial fluid reduce the lubricating ability of the joint and can lead to propagation of cartilage wear. Clinically approved viscosupplements are aimed at restoring synovial fluid lubricity and reducing the inflammatory response, but their efficacy remains nebulous. Enhanced viscosupplements combine sodium hyaluronate with additional materials (such as glucocorticoids and antioxidants) that target specific aspects of osteoarthritis, but the benefits of these additions seem minimal. Tribosupplementation, the delivery of non-hyaluronan-based lubricants to the joint, shows some promise but is largely in the preclinical stages of development; this approach includes fluid additives and matrix enhancers. Fluid additives are cartilage lubricants (with a linear, hydrogel or particle structure) that remain suspended in the synovial fluid following intraarticular injection and comprise linear, hydrogel and particle structures. Matrix enhancers are cartilage lubricants (with a linear, hydrogel or particle structure) that, in addition to containing a lubricious domain, contain a domain that binds to the cartilage surface. [ABSTRACT FROM AUTHOR]

Bone microdamage is common at subchondral bone (SCB) sites subjected to repeated high rate and magnitude of loading in the limbs of athletic animals and humans. Microdamage can affect the biomechanical behaviour of bone under physiological loading conditions. To understand the effects of microdamage on the mechanical properties of SCB, it is important to be able to quantify it. The extent of SCB microdamage had been previously estimated qualitatively using plain microcomputed tomography (μCT) and a radiocontrast quantification method has been used for trabecular bone but this method may not be directly applicable to SCB due to differences in bone structure. In the current study, SCB microdamage detection using lead uranyl acetate (LUA) and quantification by contrast‐enhanced μCT and backscattered scanning electron microscopy (SEM) imaging techniques were assessed to determine the specificity of the labels to microdamage and the accuracy of damaged bone volume metrices. SCB specimens from the metacarpus of racehorses, with the hyaline articular cartilage (HAC) removed, were grouped into two with one group subjected to ex vivo uniaxial compression loading to create experimental bone damage. The other group was not loaded to preserve the pre‐existing in vivo propagated bone microdamage. A subset of each group was stained with LUA using an established or a modified protocol to determine label penetration into SCB. The μCT and SEM images of stained specimens showed that penetration of LUA into the SCB was better using the modified protocol, and this protocol was repeated in SCB specimens with intact hyaline articular cartilage. The percentage of total label localised to bone microdamage was determined on SEM images, and the estimated labelled bone volume determined by μCT in SCB groups was compared. Label was present around diffuse and linear microdamage as well as oblique linear microcracks present at the articular surface, except in microcracks with high‐density mineral infills. Bone surfaces lining pores with recent mineralisation were also labelled. Labelled bone volume fraction (LV/BV) estimated by μCT was higher in the absence of HAC. At least 50% of total labels were localised to bone microdamage when the bone area fraction (B.Ar/T.Ar) of the SCB was greater than 0.85 but less than 30% when B.Ar/T.Ar of the SCB was less than 0.85. To adjust for LUA labels on bone surfaces, a measure of the LV/BV corrected for bone surface area (LV/BV BS−1) was used to quantify damaged SCB. In conclusion, removal of HAC and using a modified labelling protocol effectively stained damaged SCB of the metacarpus of racehorses and represents a technique useful for quantifying microdamage in SCB. This method can facilitate future investigations of the effects of microdamage on joint physiology. [ABSTRACT FROM AUTHOR]

We aimed to investigate the relationship between quantitative evaluation by compositional MRI, including T1ρ, and histological and macroscopic assessments, to verify the validity of compositional MRI, and examine the relationship between compositional MRI evaluation reconstructed in three dimensions (3D) and histological and visual assessments. Twenty-seven patients with knee osteoarthritis underwent T1ρ and T2 magnetic resonance imaging (MRI). Histological and gross tissue evaluations were performed on the excised bone sections of total knee arthroplasty. Semi-quantitative histological evaluation of tissue changes were assessed by measuring the optical density of digitally captured safranin O-stained and Collagen type II antibody-stained paraffin sections. Macroscopic cartilage severity was determined on a 5-grade scale (G0–G5). T1ρ and T2 values (3D and 2D), and their correlation with each of these parameters were investigated. 3D T1 ρ is negatively correlated with histological evaluations and positively correlated with visual assessments. Only 3D T1ρ values correlated with histological quantitative evaluation (Safranin-O staining; r = −0.53, P = 0.014, Collagen type II antibody staining; r = −0.60, P = 0.019). 2D T1ρ and 3D, 2D T2 values did not correlate with histological evaluation results. Macroscopic cartilage severity grade correlated with all T1ρ and T2 values (3D T1ρ; r = 0.61, P < 0.001, 2D T1ρ; r = 0.52, P < 0.001, 3D T2; r = 0.33, P = 0.045, 2D T2; r = 0.41, P = 0.01). 3D T1ρ mapping reflects the changes in the molecular structure of the cartilage matrix that occur in arthropathic changes and may be an effective tool for detecting cartilage degeneration. • Radiography cannot effectively quantify cartilage degeneration. • It cannot also assess the degree of degenerative changes in the cartilage in situ in early knee OA. • We aimed to histologically validate 3D T1ρ mapping for these purposes. • 3D T1ρ values were negatively correlated with pathological staining levels. • This is the first study to histologically assess the validity of 3D compositional MRI evaluation. [ABSTRACT FROM AUTHOR]

The outcome of hand fractures correlates closely with the severity of initial injury. The risk factors include injuries of the tendons and tendon sheaths, damage of the articular cartilage, comminution of fractures, severely crushed soft tissues, bone loss, aggressive surgical dissection, delay of treatment, and the implant itself. On admission, demographic data was recorded and a thorough history was taken to assess mode of injury and associated co-morbidities. General systematic and local examination were done to assess other associated injuries and open wounds followed by radiological evaluation in AP and oblique views. Functional outcome assessed by ASSH (American Society for Surgery of the Hand) TAF (Total Active Flexion) score was excellent in 22 patients (73%), good in 6 patients (20%), fair in 2 patient (6%). The overall results are satisfactory. [ABSTRACT FROM AUTHOR]

Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical treatment, the rising gene therapy is able to have a durable effect on tissue regeneration, such as impaired bone regeneration, articular cartilage repair and cancer-resected tissue repair. Gene therapy can also facilitate the production of in situ therapeutic factors, thus minimizing the diffusion or loss of gene complexes and enabling spatiotemporally controlled release of gene products for tissue regeneration. Among different gene delivery vectors and supportive gene-activated matrices, advanced gene/drug nanocarriers attract exceptional attraction due to their tunable physiochemical properties, as well as excellent adaptive performance in gene therapy for tissue regeneration, such as bone, cartilage, blood vessel, nerve and cancer-resected tissue repair. This paper reviews the recent advances on nonviral-mediated gene delivery systems with an emphasis on the important role of advanced nanocarriers in gene therapy and tissue regeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the deepening of the aging of the world population, the prevalence rate of osteoarthritis is increasing. In recent years, more and more attention has been paid to the study of osteoarthritis. Studies have shown that autophagy and apoptosis are strongly associated with the occurrence and development of osteoarthritis, and play an important role in it. OBJECTIVE: To review the molecular mechanisms of the interaction between autophagy and apoptosis in osteoarthritis, aiming to explore the relationship between autophagy and apoptosis in osteoarthritis and the coupling mechanism of the two to mediate the occurrence and development of osteoarthritis, so as to provide new ideas for the treatment of osteoarthritis. METHODS: The Chinese and English key words “osteoarthritis, autophagy, apoptosis” were searched in the CNKI and PubMed. After screening by reading the title, abstract and key words, the relevant literature was carefully read. After excluding studies unrelated to the content of the paper and repetitive studies, 68 articles were finally included for the summary. RESULTS AND CONCLUSION: (1) The occurrence and development of osteoarthritis are related to autophagy and apoptosis of chondrocytes. Autophagy protects chondrocytes from stress damage, but excessive autophagy also induces or promotes chondrocyte apoptosis and reduces the survival rate of chondrocytes. The two perturb each other to regulate the degeneration of articular cartilage. (2) miRNA, Beclin-1 and oxidative stress are all involved in the regulation of autophagy and apoptosis on osteoarthritis, and affect the development of osteoarthritis. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using autologous matrix-induced chondrogenesis (AMIC), while also discussing the mid-long term functional outcomes, complications, and surgical failure rate. Methods: We searched Embase, PubMed, and Web of Science for studies on OLT treated with AMIC with an average follow-up of at least 2 years. Publication information, patient data, functional scores, surgical failure rate, and complications were extracted. Results: A total of 15 studies were screened and included, with 12 case series selected for meta-analysis and 3 non-randomized controlled studies chosen for descriptive analysis. The improvements in the Visual Analog Scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot, and Tegner scores at the last follow-up were (SMD = − 2.825, 95% CI − 3.343 to − 2.306, P < 0.001), (SMD = 2.73, 95% CI 1.60 to 3.86, P < 0.001), (SMD = 0.85, 95% CI 0.5 to 1.2, P < 0.001) respectively compared to preoperative values. The surgery failure rate was 11% (95% CI 8–15%), with a total of 12 patients experiencing complications. Conclusion: The use of AMIC demonstrates a positive impact on pain management, functional improvement, and mobility enhancement in patients with OLT. It is worth noting that the choice of stent for AMIC, patient age, and OLT size can influence the ultimate clinical outcomes. This study provides evidences supporting the safety and efficacy of AMIC as a viable treatment option in real-world medical practice. [ABSTRACT FROM AUTHOR]

Early diagnosis of post‐traumatic osteoarthritis (PTOA) is critical for designing better treatments before the degradation becomes irreversible. We utilized multimodal high‐resolution imaging to investigate early‐stage deterioration in articular cartilage and the subchondral bone plate from a sub‐critical impact to the knee joint, which initiates PTOA. The knee joints of 12 adult rabbits were mechanically impacted once on the femoral articular surface to initiate deterioration. At 2‐ and 14‐week post‐impact surgery, cartilage‐bone blocks were harvested from the impact region in the animals (N = 6 each). These blocks were assessed for deterioration using polarized light microscopy (PLM), microcomputed tomography (μCT), and biochemical analysis. Statistically significant changes were noted in the impact tissues across the calcified zone (CZ) at 14 weeks post‐impact: the optical retardation values in the CZ of impact cartilage had a drop of 29.0% at 14 weeks, while the calcium concentration in the CZ of impact cartilage also had a significant drop at 14 weeks. A significant reduction of 6.3% in bone mineral density (BMD) was noted in the subchondral bone plate of the impact samples at 14 weeks. At 2 weeks post‐impact, only minor, non‐significant changes were measured. Furthermore, the impact knees after 14 weeks had greater structural changes compared with the 2‐week impact knees, indicating progressive degradation over time. The findings of this study facilitated a connection between mineralization alterations and the early deterioration of knee cartilage after a mechanical injury. In a broader context, these findings can be beneficial in improving clinical strategies to manage joint injuries. [ABSTRACT FROM AUTHOR]

Background: Mechanical unloading of the knee articular cartilage results in cartilage matrix atrophy, signifying the osteoarthritic-inductive potential of mechanical unloading. In contrast, mechanical loading stimulates cartilage matrix production. However, little is known about the response of meniscal fibrocartilage, a major mechanical load-bearing tissue of the knee joint, and its functional matrix-forming fibrochondrocytes to mechanical unloading events. Methods: In this study, primary meniscus fibrochondrocytes isolated from the inner avascular region of human menisci from both male and female donors were seeded into porous collagen scaffolds to generate 3D meniscus models. These models were subjected to both normal gravity and mechanical unloading via simulated microgravity (SMG) for 7 days, with samples collected at various time points during the culture. Results: RNA sequencing unveiled significant transcriptome changes during the 7-day SMG culture, including the notable upregulation of key osteoarthritis markers such as COL10A1, MMP13, and SPP1, along with pathways related to inflammation and calcification. Crucially, sex-specific variations in transcriptional responses were observed. Meniscus models derived from female donors exhibited heightened cell proliferation activities, with the JUN protein involved in several potentially osteoarthritis-related signaling pathways. In contrast, meniscus models from male donors primarily regulated extracellular matrix components and matrix remodeling enzymes. Conclusion: These findings advance our understanding of sex disparities in knee osteoarthritis by developing a novel in vitro model using cell-seeded meniscus constructs and simulated microgravity, revealing significant sex-specific molecular mechanisms and therapeutic targets. [ABSTRACT FROM AUTHOR]

Purpose: Facet joint degeneration (FJD) is a major cause of low back pain. Parathyroid hormone (PTH) (1–34) is commonly used to treat osteoporosis. However, little is known about its effects on FJD induced by estrogen deficiency. This study aims to investigate the effects of PTH (1–34) on FJD induced by estrogen deficiency and the underlying pathogenesis of the disease. Methods: Forty 3-month-old female Sprague-Dawley rats were randomly divided into four groups: 30 received bilateral ovariectomy (OVX) followed by 12 weeks of treatment with normal saline, PTH (1–34) or 17β-estradiol (E2), and 10 received sham surgery followed by administration of normal saline. Status and Wnt/β-catenin signaling activity in the cartilage and subchondral bone of the L4–L5 FJs and serum biomarkers were analyzed. Results: Administration of PTH (1–34) and E2 ameliorated cartilage lesions, and significantly decreased MMP-13 and caspase-3 levels and chondrocyte apoptosis. PTH (1–34) but not E2 significantly increased cartilage thickness, number of chondrocytes, and the expression of aggrecan. PTH (1–34) significantly improved microarchitecture parameters of subchondral bone, increased the expression of collagen I and osteocalcin, and decreased RANKL/OPG ratio. E2 treatment significantly increased the OPG level and decreased the RANKL/OPG ratio in the subchondral bone of ovariectomized rats, but it did not significantly improve the microarchitecture parameters of subchondral bone. Wnt3a and β-catenin expression was significantly reduced in the articular cartilage and subchondral bone in OVX rats, but PTH (1–34) could increase the expression of these proteins. E2 significantly increased the activity of Wnt/β-catenin pathway only in cartilage, but not in subchondral bone. The restoration of Wnt/β-catenin signaling had an obvious correlation with the improvement of some parameters associated with the FJs status. Conclusion: Wnt/β-catenin signaling may be a potential therapeutic target for FJD induced by estrogen deficiency. PTH (1–34) is effective in treating this disease with better efficacy than 17β-estradiol, and the efficacy may be attributed to its restoration of Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (OA) and obesity are major public health concerns that are closely intertwined. This intimate relationship was documented by considering obesity as the most significant preventable risk factor associated with knee OA. To date, however, the effects of obesity on the knee joint's passive-active structure and cartilage loading have been inconclusive. Hence, this study investigates the intricate relationship between obesity and knee OA, centering on the biomechanical changes in knee joint active and passive reactions during the stance phase of gait. Using a subject-specific musculoskeletal and finite element approach, muscle forces, ligament stresses, and articular cartilage contact stresses were analyzed among 60 individuals with different body mass indices (BMI) classified under healthy weight, overweight, and obese categories. Our predicted results showed that obesity significantly influenced knee joint mechanical reaction, increasing muscle activations, ligament loading, and articular cartilage contact stresses, particularly during key instances of the gait cycle—first and second peak loading instances. The study underscores the critical role of excessive body weight in exacerbating knee joint stress distribution and cartilage damage. Hence, the insights gained provide a valuable biomechanical perspective on the interaction between body weight and knee joint health, offering a clinical utility in assessing the risks associated with obesity and knee OA. [ABSTRACT FROM AUTHOR]

The incidence of large bone and articular cartilage defects caused by traumatic injury is increasing worldwide; the tissue regeneration process for these injuries is lengthy due to limited self‐healing ability. Endogenous bioelectrical phenomenon has been well recognized to play an important role in bone and cartilage homeostasis and regeneration. Studies have reported that electrical stimulation (ES) can effectively regulate various biological processes and holds promise as an external intervention to enhance the synthesis of the extracellular matrix, thereby accelerating the process of bone and cartilage regeneration. Hence, electroactive biomaterials have been considered a biomimetic approach to ensure functional recovery by integrating various physiological signals, including electrical, biochemical, and mechanical signals. This review will discuss the role of endogenous bioelectricity in bone and cartilage tissue, as well as the effects of ES on cellular behaviors. Then, recent advances in electroactive materials and their applications in bone and cartilage tissue regeneration are systematically overviewed, with a focus on their advantages and disadvantages as tissue repair materials and performances in the modulation of cell fate. Finally, the significance of mimicking the electrophysiological microenvironment of target tissue is emphasized and future development challenges of electroactive biomaterials for bone and cartilage repair strategies are proposed. [ABSTRACT FROM AUTHOR]

Articular cartilage and meniscus transfer and distribute mechanical loads in the knee joint. Degeneration of these connective tissues occurs during the progression of knee osteoarthritis, which affects their composition, microstructure, and mechanical properties. A deeper understanding of disease progression can be obtained by studying them simultaneously. Time‐resolved synchrotron‐based X‐ray phase‐contrast tomography (SR‐PhC‐µCT) allows to capture the tissue dynamics. This proof‐of‐concept study presents a rheometer setup for simultaneous in situ unconfined compression and SR‐PhC‐µCT of connective knee tissues. The microstructural response of bovine cartilage (n = 16) and meniscus (n = 4) samples under axial continuously increased strain, or two steps of 15% strain (stress–relaxation) is studied. The chondrocyte distribution in cartilage and the collagen fiber orientation in the meniscus are assessed. Variations in chondrocyte density reveal an increase in the top 40% of the sample during loading, compared to the lower half. Meniscus collagen fibers reorient perpendicular to the loading direction during compression and partially redisperse during relaxation. Radiation damage, image repeatability, and image quality assessments show little to no effects on the results. In conclusion, this approach is highly promising for future studies of human knee tissues to understand their microstructure, mechanical response, and progression in degenerative diseases. [ABSTRACT FROM AUTHOR]

Introduction: Charcot arthropathy is a progressive disorder of the ankle and foot joints that can lead to foot deformity and instability. Surgical intervention is often necessary for deformity and ulcer management during the chronic phase. The device used for arthrodesis remains a challenge. Methods: This clinical trial study included diabetic patients aged 40 years or older with Charcot foot. Lateral approach with lateral malleolar osteotomy was used to access the ankle joints and remove the cartilage. A small incision was made on the plantar aspect of the foot to pass an appropriately sized intramedullary nail. Demographic information, medical history, surgical details and Clinical data were collected at 2-week and 1-year follow-ups using the Ankle-Hindfoot Scale (AOFAS) score and the EuroQol 5-Dimensional 5-Level (EQ-5D-5L) health utility score. Results: Twenty-six patients with a mean age of 63 ± 0.23 years were included in the study. The findings showed significant improvements in AOFAS questionnaire items related to pain score, length of the walk, walking surfaces, walking disorders, sagittal alignment, back leg alignment, sustainability, alignment and the total score (P value < 0.001). The EQ-5D-5L questionnaire also showed a significant improvement in the total score (P value = 0.002). Conclusion: This study provides evidence supporting the effectiveness of tibiotalocalcaneal arthrodesis by hindfoot nailing in diabetic patients with Charcot foot joints and demonstrated comparable and superior outcomes in terms of patient satisfaction and complication rate when compared to previous studies. [ABSTRACT FROM AUTHOR]

This article discusses a study that aimed to assess the association between knee cartilage T2 values and age, sex, and cartilage lesions. The study involved 929 subjects aged 28 to 89 years who underwent MRI scans. The results showed that T2 values were higher in subjects with osteoarthritis (OA) risk factors and cartilage lesions compared to those without. There was also significant variation in T2 values between different joint compartments, with the highest values in femoral cartilage and the lowest in tibial cartilage. The study established a reference database of T2 values for subjects with normal cartilage morphology and without evidence of cartilage degeneration or OA risk factors. [Extracted from the article]

This article evaluates the long-term outcomes of matrix-induced autologous chondrocyte implantation (MACI) for knee cartilage injuries. Twenty-six patients were treated with MACI and underwent magnetic resonance (MR) arthrography and clinical examinations at midterm and long term after surgery. The results showed that while imaging studies indicated deterioration of the grafts, the patients did not experience significant clinical deterioration. The decrease in clinical scores was not significant, but modified MOCART scores decreased significantly. Overall, MACI appears to be a viable treatment option for knee cartilage injuries. [Extracted from the article]

Degenerative joint disease is a dynamic pathological process characterised by a destabilisation of the degradation and synthesis processes of articular cartilage and subchondral bone layer. Studies suggest that individuals with gonarthrosis experience deficits in proprioception, in addition to changes within their joints, which directly affects their ability to maintain posture and increases their risk of falling. Objectives: The aim of this study was to assess the functional status of patients with gonarthrosis through a posturographic examination conducted on a stabilometric platform (force plate) and a functional clinical examination. Methods: Participants were divided into two groups—a control group (n = 125) and a study group (n = 125). During the qualification process, subjective and objective examinations were conducted, including a functional assessment by means of such tests as the "Up and Go" Test, Functional Reach Test, Five Time Sit to Stand Test, and the Step Test. Subsequently, an assessment was conducted on the force plate by means of a posturographic test—the Romberg test performed with open and closed eyes in a standing position—and balance was evaluated using the Berg Balance Scale. The obtained data were analysed with the use of the IBM SPSS Statistics software version 27.0, by means of the Mann–Whitney test, and correlations were determined by means of Spearman's test. A significance level of p = 0.05 was adopted. Results: Statistically significant differences were observed among the assessed groups as a result of both functional and posturographic examinations, along with positive correlations for disease duration, age, and BMI index. Conclusions: Patients with gonarthrosis exhibited disturbances in balance, functionality, and posture compared to healthy individuals in the control group. [ABSTRACT FROM AUTHOR]

Background: Although individuals with anterior cruciate ligament reconstruction (ACLR) are at high risk for posttraumatic osteoarthritis, mechanisms underlying the relationship between running and knee cartilage health remain unclear. Objective: We aimed to investigate how 30 min of running influences femoral cartilage thickness and composition and their relationships with running biomechanics in patients with ACLR and controls. Methods: Twenty patients with ACLR (time post‐ACLR: 14.6 ± 6.1 months) and 20 matched controls participated in the study. A running session required both groups to run for 30 min at a self‐selected speed. Before and after running, we measured femoral cartilage thickness via ultrasound imaging. A MRI session consisted of T2 mapping. Results: The ACLR group showed longer T2 relaxation times in the medial femoral condyle at resting compared with the control group (central: 51.2 ± 16.6 vs. 34.9 ± 13.2 ms, p = 0.006; posterior: 50.2 ± 10.1 vs. 39.8 ± 7.4 ms, p = 0.006). Following the run, the ACLR group showed greater deformation in the medial femoral cartilage than the control group (0.03 ± 0.01 vs. 0.01 ± 0.01 cm, p = 0.001). Additionally, the ACLR group showed significant negative correlations between resting T2 relaxation time in the medial femoral condyle and vertical impulse (standardized regression coefficients = −0.99 and p = 0.004) during running. Conclusions: Our findings suggest that those who are between 6 and 24 months post‐ACLR have degraded cartilage composition and their cartilage deforms more due to running vGRF. [ABSTRACT FROM AUTHOR]

Regenerative cartilage procedures have become increasingly more important in the reconstructive treatment of acute and chronic chondral and osteochondral lesions in the knee joint. Depending on the size and depth of the defect standard methods with high evidence and potential methods with rather low evidence have been established. Long-term results determine the success and failure of the applied procedures and are being discussed in this CME article. [ABSTRACT FROM AUTHOR]

The case presentation describes a joint-preserving procedure for pre-existing focal cartilage damage to the shoulder joint with the onset of osteoarthritis in a young female patient with high sporting demands. A significant improvement in quality of life was achieved after an observation period of two years. Imaging morphology shows good cartilage regeneration in the PD sequences in the MRI after application of matrix-augmented bone marrow stimulation using a hyaluronic acid matrix. The clinical and morphological results offer hope for future success in delaying shoulder joint replacement. [ABSTRACT FROM AUTHOR]

Modern pre- and post-operative rehabilitation is geared towards structural damage, functional limitations and concomitant comorbidity. In addition, the cognitive-emotional situation of those affected and their life situation (family, work, sport) must be taken into account. In order to meet the requirement of patientcentered rehabilitation, all possible measures should therefore be adapted to the individual based on clinical and functional criteria. Off-the-shelf follow-up treatment is therefore neither realistic nor effective. Nevertheless, phase models have become established in practice. These create a rough time frame that can be seen as a guide for rehabilitation after cartilage regenerative surgery. In addition to preoperative preparation, the focus is on progressively increasing the load and training the main forms of motor basic skills - mobility, endurance, coordination and strength. [ABSTRACT FROM AUTHOR]

The current approach to the clinical management of osteoarthritis is to alleviate symptoms arising from late-stage disease. Early stage or pre-arthritic disease is clinically silent as structural changes typically precede the clinical signs and symptoms of pain, deformity, functional limitations and disability. Biological and surgical therapeutic approaches to this include platelet-rich plasma (PRP), stromal cells or bone marrow aspirates (BMAC) and hyaluronic acid (HA) as a conservative treatment or support of a surgical cartilage procedure to optimize the cartilage regenerate tissue. The following article provides a condensed overview. [ABSTRACT FROM AUTHOR]

General principles of cartilage repair therapies have not changed in the last years. Recommendations for cartilage repair include symptomatic ICRS grade 3 and 4 classified cartilage defects. However, what has changed in the last years is a better understanding of underlying or concomitant pathologies. Since a more precise analysis and stringent therapy of concomitant pathologies has been performed, an increase in success rates especially in formerly difficult entities could be observed. The most important concomitant pathologies in cartilage therapies of the hip-, knee- and ankle joint are axis deviations, instabilities, meniscus pathologies or prearthrotic deformities like hip dysplasia and femuroacetabular impingement syndrome. To increase the efficiency of cartilage repair procedures these pathologies should be corrected either prior to, or at latest concomitant to any cartilage repair surgery. Therefore, this article is intended to give an overview of the most important concomitant pathologies in cartilage repair of the lower extremities and their possibilities of correction. [ABSTRACT FROM AUTHOR]

Stage-appropriate treatment of joint cartilage damage aims to improve joint function and slow down or prevent the development of osteoarthritis. A deep understanding of biomechanical influences has led to more precise preoperative analyses, allowing for individual adjustment of therapies. Patient-specific factors such as age and activity level are considered. Diagnostic procedures like detailed medical history and modern imaging are essential to determine the extent of damage and plan effective treatment accurately. [ABSTRACT FROM AUTHOR]

Cartilage, a flexible and smooth connective tissue that envelops the surfaces of synovial joints, relies on chondrocytes for extracellular matrix (ECM) production and the maintenance of its structural and functional integrity. Melatonin (MT), renowned for its anti-inflammatory and antioxidant properties, holds the potential to modulate cartilage regeneration and degradation. Therefore, the present study was devoted to elucidating the mechanism of MT on chondrocytes. The in vivo experiment consisted of three groups: Sham (only the skin tissue was incised), Model (using the anterior cruciate ligament transection (ACLT) method), and MT (30 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage, synovium, and subchondral bone were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via Enzyme-linked immunosorbent assay (ELISA) assays. In in vitro experiments, primary chondrocytes were divided into Control, Model, MT, negative control, and inhibitor groups. Western blotting (WB) and Quantitative RT-PCR (q-PCR) were used to detect Silent information regulator transcript-1 (SIRT1)/Nuclear factor kappa-B (NF-κB)/Nuclear factor erythroid-2-related factor 2 (Nrf2)/Transforming growth factor-beta (TGF-β)/Bone morphogenetic proteins (BMPs)-related indicators. Immunofluorescence (IF) analysis was employed to examine the status of type II collagen (COL2A1), SIRT1, phosphorylated NF-κB p65 (p-p65), and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2). In vivo results revealed that the MT group exhibited a relatively smooth cartilage surface, modest chondrocyte loss, mild synovial hyperplasia, and increased subchondral bone thickness. ICH results showed that MT downregulated the expression of components related to matrix degradation. ELISA results showed that MT reduced serum inflammatory cytokine levels. In vitro experiments confirmed that MT upregulated the expression of SIRT1/Nrf2/TGF-β/BMPs while inhibiting the NF-κB pathway and matrix degradation-related components. The introduction of the SIRT1 inhibitor Selisistat (EX527) reversed the effects of MT. Together, these findings suggest that MT has the potential to ameliorate inflammation, inhibit the release of matrix-degrading enzymes, and improve the cartilage condition. This study provides a new theoretical basis for understanding the role of MT in decelerating cartilage degradation and promoting chondrocyte repair in in vivo and in vitro cultured chondrocytes. [ABSTRACT FROM AUTHOR]

Post-traumatic osteoarthritis of the ankle (PTOA) is frequently observed following a debilitating consequence of intra-articular ankle fractures. Numerous risk factors contribute to the pathogenesis of PTOA, including articular incongruity, joint malalignment, and concomitant soft tissue damage. Despite attempts to restore joint anatomy and manage soft tissues to avoid long-term complications after intra-articular ankle fractures, the incidence of PTOA remains markedly elevated. Inflammatory processes triggered by intra-articular ankle fractures have emerged as potential instigators that expedite the progression of PTOA. Injury to the articular cartilage and subchondral bone may lead to the release of inflammatory mediators, which can contribute to cartilage degradation and bone resorption. This study provides a narrative review on the current knowledge concerning the association between inflammation and the development of PTOA following intra-articular ankle fractures. We also discuss novel therapeutic agents that target inflammatory pathways to impede the progression of post-traumatic osteoarthritis after intra-articular ankle fractures. These medication and interventions were summarized within this review article. [ABSTRACT FROM AUTHOR]

Articular cartilage is crucial for joint function but its avascularity limits intrinsic repair, leading to conditions like osteoarthritis (OA). Chondromodulin-I (Cnmd) has emerged as a key molecule in cartilage biology, with potential implications for OA therapy. Cnmd is primarily expressed in cartilage and plays an important role in chondrocyte proliferation, cartilage homeostasis, and the blocking of angiogenesis. In vivo and in vitro studies on Cnmd, also suggest an involvement in bone repair and in delaying OA progression. Its downregulation correlates with OA severity, indicating its potential as a therapeutic target. Further research is needed to fully understand the mode of action of Cnmd and its beneficial implications for managing OA. This comprehensive review aims to elucidate the molecular characteristics of Cnmd, from its expression pattern, role in cartilage maintenance, callus formation during bone repair and association with OA. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease commonly found in elderly people and obese patients. Currently, OA treatments are determined based on their condition severity and a medical professional's advice. The aim of this study was to differentiate human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) into chondrocytes for transplantation in OA-suffering guinea pigs. hWJ-MSCs were isolated using the explant culture method, and then, their proliferation, phenotypes, and differentiation ability were evaluated. Subsequently, hWJ-MSCs-derived chondrocytes were induced and characterized based on immunofluorescent staining, qPCR, and immunoblotting techniques. Then, early-OA-suffering guinea pigs were injected with hyaluronic acid (HA) containing either MSCs or 14-day-old hWJ-MSCs-derived chondrocytes. Results showed that hWJ-MSCs-derived chondrocytes expressed specific markers of chondrocytes including Aggrecan, type II collagen, and type X collagen proteins and β-catenin, Sox9, Runx2, Col2a1, Col10a1, and ACAN gene expression markers. Administration of HA plus hWJ-MSCs-derived chondrocytes (HA-CHON) produced a better recovery rate of degenerative cartilages than HA plus MSCs or only HA. Histological assessments demonstrated no significant difference in Mankin's scores of recovered cartilages between HA-CHON-treated guinea pigs and normal articular cartilage guinea pigs. Transplantation of hWJ-MSCs-derived chondrocytes was more effective than undifferentiated hWJ-MSCs or hyaluronic acid for OA treatment in guinea pigs. This study provides a promising treatment to be used in early OA patients to promote recovery and prevent disease progression to severe osteoarthritis. [ABSTRACT FROM AUTHOR]

Joint-resident chondrogenic precursor cells have become a significant therapeutic option due to the lack of regenerative capacity in articular cartilage. Progenitor cells are located in the superficial zone of the articular cartilage, producing lubricin/Prg4 to decrease friction of cartilage surfaces during joint movement. Prg4-positive progenitors are crucial in maintaining the joint's structure and functionality. The disappearance of progenitor cells leads to changes in articular hyaline cartilage over time, subchondral bone abnormalities, and the formation of ectopic ossification. Genetic labeling cell technology has been the main tool used to characterize Prg4-expressing progenitor cells of articular cartilage in vivo through drug injection at different time points. This technology allows for the determination of the origin of progenitor cells and the tracking of their progeny during joint development and cartilage damage. We endeavored to highlight the currently known information about the Prg4-producing cell population in the joint to underline the significance of the role of these cells in the development of articular cartilage and its homeostasis. This review focuses on superficial progenitors in the joint, how they contribute to postnatal articular cartilage formation, their capacity for regeneration, and the consequences of Prg4 deficiency in these cells. We have accumulated information about the Prg4+ cell population of articular cartilage obtained through various elegantly designed experiments using transgenic technologies to identify potential opportunities for further research. [ABSTRACT FROM AUTHOR]

Objective: Early articular cartilage lesion (CL) is a vital sign in the onset of posttraumatic knee osteoarthritis (PTOA) in patients with anterior cruciate ligament deficiency (ACLD). Researchers have suggested that altered kinematics could accelerate CLs and, therefore, lead to the onset of PTOA. However, little is known about whether specific knee kinematics exist that lead to early CL in chronic ACLD knees. Level walking is the most frequent and relevant in vivo activity, which greatly impacts knee health. We hypothesized that the knee kinematics during level walking in chronic ACLD knees with early tibiofemoral CL would significantly differ from those of chronic ACLD knees without early tibiofemoral CL. Methods: Thirty patients with a chronic ACLD history, including 18 subjects with CLs and 12 subjects without CLs, and 35 healthy control subjects were recruited for the study from July 2020 to August 2022. The knee kinematic data during level walking were collected using a three‐dimensional motion analysis system. The kinematic differences between groups were compared using statistical parametric mapping with one dimension for One‐Way ANOVA. The cartilage statuses of the ACLD knees were assessed via MRI examination. The CLs distribution of subjects was evaluated using a modified Noyes scale and analyzed by chi‐square tests. Results: ACLD knees with CLs had significantly greater posterior tibial translation (7.7–8.0mm, 12%–18% gait cycle GC, p = 0.014) compared to ACLD knees without CLs during level walking. ACLD knees with CLs had greater posterior tibial translation (4.6–5.5mm, 0%–23% GC, p < 0.001; 5.8–8.0mm, 86%–100% GC, p < 0.001) than healthy controls during level walking. In the group of ACLD knees with CLs, CL is mainly located in the back of the tibia plateau and front of load bearing area of the medial femoral condyle (p < 0.05). Conclusion: Chronic anterior cruciate ligament deficient knees with cartilage lesions have increased posterior tibial translation compared to anterior cruciate ligament deficient knees without cartilage lesions and healthy subjects. The posterior tibial translation may play an important role in knee cartilage degeneration in ACLD knees. The increased posterior tibial translation and cartilage lesion characteristics may improve our understanding of the role of knee kinematics in cartilage degeneration and could be a helpful potential reference for anterior cruciate ligament deficient therapy, such as physical training to improve abnormal kinematic behavior. [ABSTRACT FROM AUTHOR]

Authors have demonstrated that apoptosis activation is a pathway related to cartilage degradation characteristics of the OA process. Autophagy is an adaptive response to protect cells from various environmental changes, and defects in autophagy are linked to cell death. In this sense, decreased autophagy of chondrocytes has been observed in OA articular cartilage. The aim of this work was to study the role of OA mitochondria in apoptosis, autophagy, and senescence, using OA and Normal (N) transmitochondrial cybrids. Results: OA cybrids incubated with menadione showed a higher percentage of late apoptosis and necrosis than N cybrids. Stimulation of cybrids with staurosporine and IL-1β showed that OA cybrids were more susceptible to undergoing apoptosis than N cybrids. An analysis of the antioxidant response using menadione on gene expression revealed a lower expression of nuclear factor erythroid 2-like 2 and superoxide dismutase 2 in OA than N cybrids. Activation of microtubule-associated protein 1A/1B-light chain 3 was reduced in OA compared to N cybrids. However, the percentage of senescent cells was higher in OA than N cybrids. Conclusion: This work suggests that mitochondria from OA patients could be involved in the apoptosis, autophagy, and senescence of chondrocytes described in OA cartilage. [ABSTRACT FROM AUTHOR]

Articular cartilage was expected to be one of the first successfully engineered tissues, but today, cartilage repair products are few and they exhibit considerable limitations. For example, of the cell-based products that are available globally, only one is marketed for non-knee indications, none are indicated for severe osteoarthritis or rheumatoid arthritis, and only one is approved for marketing in the USA. However, advances in cartilage tissue engineering might now finally lead to the development of new cartilage repair products. To understand the potential in this field, it helps to consider the current landscape of tissue-engineered products for articular cartilage repair and particularly cell-based therapies. Advances relating to cell sources, bioactive stimuli and scaffold or scaffold-free approaches should now contribute to progress in therapeutic development. Engineering for an inflammatory environment is required because of the need for implants to withstand immune challenge within joints affected by osteoarthritis or rheumatoid arthritis. Bringing additional cartilage repair products to the market will require an understanding of the translational vector for their commercialization. Advances thus far can facilitate the future translation of engineered cartilage products to benefit the millions of patients who suffer from cartilage injuries and arthritides. In this Review, the current landscape of tissue engineering for repair of articular cartilage is discussed, with reference to advances in cell sources, bioactive stimuli and the use of scaffolds, and with consideration of the challenges that result from the inflammatory articular environments in osteoarthritis and rheumatoid arthritis. Key points: Of the cell-based articular cartilage products available globally, only one is marketed for non-knee indications, none are marketed for severe osteoarthritis and none are marketed for rheumatoid arthritis. Cartilage tissue engineering advances include making scaffold-based and scaffold-free cartilage with robust mechanical properties that might enable implants to survive in the loaded-joint environment. Tissue engineering cartilage implants to survive the inflammatory environment through the use of immunomodulatory biomaterials and synthetic biology is a current research highlight. Most large-animal studies for cartilage tissue engineering in the knee use porcine, caprine and ovine models, whereas porcine models are used for temporomandibular joint studies. Several tissue-engineered cartilage products in clinical development use allogeneic cell sources; the use of cell banks that employ allogeneic cells can improve reproducibility and consistency. Owing to the arduous nature of translating biologics, academic researchers should familiarize themselves with the translational vector (including regulatory, manufacturing, funding and intellectual property aspects) to facilitate clinical development. [ABSTRACT FROM AUTHOR]

With rates growing quickly with age, osteoarthritis (OA) is the most common cause of chronic disability in aging persons. The discomfort and reduced motion associated with osteoarthritis have a significant impact on quality of life, and there is no known solution. Runt-related transcription factor 1(Runx1) has been shown to play a protective role in the development of osteoarthritis by promoting chondrogenesis. We had created models of ageing mice with osteoarthritis by anterior cruciate ligament transection (ACLT) and analyzed the effects of intra-articular injection of adeno-associated virus/Runx1 (AAV/Runx1) on the models. The results showed that the AAV/Runx1-group maintained better articular cartilage integrity and retained more proteoglycan than the OA group after injection of AAV-Runx1. The markers related to pathological changes in cartilage were downregulated, while the markers related to physiological changes in cartilage were upregulated. This suggests that Runx1 may impede OA progression on the knee joint of ageing mice, potentially playing a protective role in OA and becoming a probable treatment target for osteoarthritis among ageing patients in the future. [ABSTRACT FROM AUTHOR]

Osteoporosis is a chronic disease characterized by reduced bone mass and increased fracture risk, estimated to affect over 10 million people in the United States alone. Drugs used to treat bone loss often come with significant limitations and/or long‐term safety concerns. Proteoglycan‐4 (PRG4, also known as lubricin) is a mucin‐like glycoprotein best known for its boundary lubricating function of articular cartilage. In more recent years, it has been shown that PRG4 has anti‐inflammatory properties, contributes to the maintenance of subchondral bone integrity, and patients with PRG4 mutations are osteopenic. However, it remains unknown how PRG4 impacts mechanical and material properties of bone. Therefore, our objective was to perform a phenotyping study of bone in a Prg4 gene trap (GT) mouse (PRG4 deficient). We found that femurs of Prg4 GT mice have altered mechanical, structural, and material properties relative to wildtype littermates. Additionally, Prg4 GT mice have a greater number of calvarial osteoclasts than wildtype mice, but do not have a notable inflammatory serum profile. Finally, Prg4 GT mice do not have an altered rate of bone formation, and exogenous recombinant human PRG4 (rhPRG4) administration inhibited osteoclastogenesis in vitro, suggesting that the skeletal phenotype may be due to changes in bone resorption. Overall, this work demonstrates that PRG4 deficiency affects several integral properties of bone structure, mechanics, and skeletal cell activity, and provides the foundation and insight toward future work evaluating PRG4 as a potential therapeutic target in treating bone loss. [ABSTRACT FROM AUTHOR]

OBJECTIVE Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. ANIMALS 8 healthy horses. METHODS In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed. RESULTS There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240. CLINICAL RELEVANCE Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic chondrolysis of the hip is characterized by the loss of the articular cartilage of the hip joint with spectrum ranging from full recovery to fibrous ankylosis. Study assessed outcomes following intra-articular steroid injections, joint manipulation and traction immobilization. Methods: Retrospective (2012–2021) review of 41 cases treated for idiopathic chondrolysis of hip, assessed pre-operatively and post-operatively (minimum 2-year follow-up) using Children's Hospital Oakland Hip Evaluation Score (CHOHES), visual analogue scale (VAS) and range of motion measurements. Results: Twenty-five patients (62%) achieved painless mobility, 6 (14%) had hip stiffness without pain and 10 (24%) had painful and stiff hips at final follow-up. They had a mean age of 12.49 ± 2.4 years and a mean follow-up duration of 33.15 ± 13.1 months. Range of motion improved significantly (p < 0.05). VAS improved to 3.93 ± 1.3 from 7.8 ± 0.7. CHOHES improved from 29.12 ± 9.9 to 56.37 ± 17.6. Conclusion: Intra-articular steroid injection, manipulation and traction immobilization may effectively treat idiopathic chondrolysis of the hip by enhancing patient function and reducing the need for further surgical intervention. [ABSTRACT FROM AUTHOR]

One of the most common musculoskeletal disorders, osteoarthritis (OA), causes worldwide disability, morbidity, and poor quality of life by degenerating articular cartilage, modifying subchondral bone, and inflaming synovial membranes. OA pathogenesis pathways must be understood to generate new preventative and disease-modifying therapies. In recent years, it has been acknowledged that gut microbiota (GM) can significantly contribute to the development of OA. Dysbiosis of GM can disrupt the "symphony" between the host and the GM, leading to a host immunological response that activates the "gut–joint" axis, ultimately worsening OA. This narrative review summarizes research supporting the "gut–joint axis" hypothesis, focusing on the interactions between GM and the immune system in its two main components, innate and adaptive immunity. Furthermore, the pathophysiological sequence of events that link GM imbalance to OA and OA-related pain is broken down and further investigated. We also suggest that diet and prebiotics, probiotics, nutraceuticals, exercise, and fecal microbiota transplantation could improve OA management and represent a new potential therapeutic tool in the light of the scarce panorama of disease-modifying osteoarthritis drugs (DMOADs). Future research is needed to elucidate these complex interactions, prioritizing how a particular change in GM, i.e., a rise or a drop of a specific bacterial strain, correlates with a certain OA subset to pinpoint the associated signaling pathway that leads to OA. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic joint disease characterized by irreversible cartilage degradation. Current clinical treatment options lack effective pharmaceutical interventions targeting the disease's root causes. MMP (matrix metalloproteinase) inhibitors represent a new approach to slowing OA progression by addressing cartilage degradation mechanisms. However, very few drugs within this class are in preclinical or clinical trial phases. Hydrogel-based 3D in vitro models have shown promise as preclinical testing platforms due to their resemblance to native extracellular matrix (ECM), abundant availability, and ease of use. Metalloproteinase-13 (MMP-13) is thought to be a major contributor to the degradation of articular cartilage in OA by aggressively breaking down type II collagen. This study focused on testing MMP-13 inhibitors using a GelMA-alginate hydrogel-based OA model induced by cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). The results demonstrate a significant inhibition of type II collagen breakdown by measuring C2C concentration using ELISA after treatment with MMP-13 inhibitors. However, inconsistencies in human cartilage explant samples led to inconclusive results. Nonetheless, the study highlights the GelMA-alginate hydrogel-based OA model as an alternative to human-sourced cartilage explants for in vitro drug screening. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine whether regular running distance and biomechanics are related to medial central femur cartilage (MCFC) structure. Methods: The cross-sectional study sample consisted of 1164 runners and nonrunners aged 18-65 yr. Participants completed questionnaires on physical activity and their running history. We performed quantitative magnetic resonance imaging of knee cartilage--T2 relaxation time (T2) mapping (high T2 indicates cartilage degeneration)--and a running biomechanical analysis using a three-dimensional motion capture system. A 14-d monitoring of the physical activity was conducted. Results: Those aged 35-49 yr were at 84% higher odds of having MCFC T2 in the highest level (85th percentile, P < 0.05) compared with youngest adults indicating that MCFC structures may be altered with aging. Being male was associated with 34% lower odds of having T2 at the highest level (P < 0.05) compared with females. Nonrunners and runners with the highest weekly running distance were more likely to have a high T2 compared with runners with running distance of 6-20 km⋅wk-1 (P < 0.05). In addition, the maximal knee internal adduction moment was associated with a 19% lower odds of having T2 at the highest level (P < 0.05). Conclusions: Females compared with males and a middle-aged cohort compared with the younger cohort seemed to be associated with the degeneration of MCFC structures. Runners who ran 6-20 km⋅wk-1 were associated with a higher quality of their MCFC compared with highly active individuals and nonrunners. Knee frontal plane biomechanics was related to MCFC structure indicating a possibility of modifying the medial knee collagen fibril network through regular running. [ABSTRACT FROM AUTHOR]

Background: The addition of an iliotibial band–based lateral extra-articular tenodesis (LET) to anterior cruciate ligament (ACL) reconstruction (ACLR) has been shown to reduce failure rates. However, there are concerns as to the potential overconstraint of tibiofemoral kinematics that may increase the risk of cartilage degradation. To date, no clinical study has investigated the effect of LET on patellofemoral joint articular cartilage health. Hypothesis: It was hypothesized that at 2 years postoperatively, (1) the addition of LET at the time of ACLR would have no effect on cartilage health on magnetic resonance imaging (MRI), and (2) higher cartilage relaxation values would be associated with worse patient-reported and functional outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: A subset of patients from the STABILITY 1 randomized controlled trial were included. All patients underwent primary ACLR with a hamstring autograft. Patients were randomized to either LET augmentation or not. Cartilage status in the patellofemoral joint between the ACLR group and ACLR+LET group was compared using 2-year postoperative quantitative MRI and the ACL osteoarthritis scores of both the surgical and the contralateral nonsurgical knees. Objective functional outcomes and patient-reported outcome measures (PROMs) were attained. Results: A total of 92 patients (43 patients in the ACLR group; mean age, 18.9 ± 3.2 years; 60.5% female; and 49 patients in the ACLR+LET group; mean age, 18.7 ± 3.2 years, 63.3% female) were included. No significant differences were seen in the mean values (ms) for adjusted T1ρ/T2 relaxation times in the medial patella (47.8/42.2 vs 47.3/43.2), central patella (45.5/42.5 vs 44.1/42.7), lateral patella (48.2/43.5 vs 47.3/43.0), medial trochlea (54.7/50.9 vs 56.4/50.9), central trochlea (53.3/51.1 vs 53.1/52.0), and lateral trochlea (54.9/52.1 vs 53.9/52.6) between the ACLR and ACLR+LET groups. No difference in overall ACL osteoarthritis scores was observed (P =.99). An increase in medial patellar T2 relaxation times was associated with a decreasing International Knee Documentation Committee score (P =.046), Knee injury and Osteoarthritis Outcome Score (KOOS) Symptoms subscale score (P =.01), and total KOOS (P =.01). Conclusion: There was no statistical difference in patellofemoral cartilage health between knees 2 years after primary ACLR with hamstring tendon autograft with or without LET. Statistically significant correlations were found between quantitative MRI relaxation times, functional outcome scores, and PROMs; however, the correlations were weak and the clinical significance is unknown. Registration: NCT02018354 (ClinicalTrials.gov identifier). [ABSTRACT FROM AUTHOR]

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N=5) and osteoarthritis (OA) (N=5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection. [ABSTRACT FROM AUTHOR]

As the most common degenerative joint disease, osteoarthritis (OA) contributes significantly to pain and disability during aging. Several genes of interest involved in articular cartilage damage in OA have been identified. However, the direct causes of OA are poorly understood. Evaluating the public human RNA-seq dataset showed that CBFB (subunit of a heterodimeric Cbfβ/Runx1, Runx2, or Runx3 complex) expression is decreased in the cartilage of patients with OA. Here, we found that the chondrocyte-specific deletion of Cbfb in tamoxifen-induced Cbfbf/f;Col2a1-CreERT mice caused a spontaneous OA phenotype, worn articular cartilage, increased inflammation, and osteophytes. RNA-sequencing analysis showed that Cbfβ deficiency in articular cartilage resulted in reduced cartilage regeneration, increased canonical Wnt signaling and inflammatory response, and decreased Hippo/Yap signaling and Tgfβ signaling. Immunostaining and western blot validated these RNA-seq analysis results. ACLT surgery-induced OA decreased Cbfβ and Yap expression and increased active β-catenin expression in articular cartilage, while local AAV-mediated Cbfb overexpression promoted Yap expression and diminished active β-catenin expression in OA lesions. Remarkably, AAV-mediated Cbfb overexpression in knee joints of mice with OA showed the significant protective effect of Cbfβ on articular cartilage in the ACLT OA mouse model. Overall, this study, using loss-of-function and gain-of-function approaches, uncovered that low expression of Cbfβ may be the cause of OA. Moreover, Local admission of Cbfb may rescue and protect OA through decreasing Wnt/β-catenin signaling, and increasing Hippo/Yap signaling and Tgfβ/Smad2/3 signaling in OA articular cartilage, indicating that local Cbfb overexpression could be an effective strategy for treatment of OA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Scaffold materials serve as platforms that provide space and structure, playing a crucial role in the regeneration of cartilage tissue. Scholars from around the world are exploring different approaches to fabricate more ideal scaffold materials. OBJECTIVE: To review the design principles and preparation methods of cartilage scaffolds, and to further explore the advantages and limitations of various preparation methods. METHODS: Literature searches were conducted on the databases of CNKI, WanFang Data, PubMed, and FMRS from 1998 to 2023. The search terms were “cartilage repair, cartilage tissue engineering, cartilage scaffold materials, preparation” in Chinese and English. A total of 57 articles were ultimately reviewed. RESULTS AND CONCLUSION: (1) The articular cartilage has a unique structure and limited self-repair capacity after injury. Even if self-repair occurs, the newly formed cartilage is typically fibrocartilage, which is far inferior to normal articular cartilage in terms of structure and mechanical properties. It is difficult to maintain normal function and often leads to degenerative changes. Currently, the design and fabrication of scaffold materials for cartilage repair need to consider the following aspects: biocompatibility and biodegradability, suitable pore structure and porosity, appropriate mechanical properties, and bioactivity. (2) Research on the preparation of cartilage scaffolds has made significant progress, continuously introducing new preparation methods and optimization strategies. These methods have their advantages and disadvantages, providing more possibilities for customized preparation and functional design of cartilage scaffolds according to specific requirements. [ABSTRACT FROM AUTHOR]

In various biological systems, analyzing how cell behaviors are coordinated over time would enable a deeper understanding of tissue-scale response to physiologic or superphysiologic stimuli. Such data is necessary for establishing both normal tissue function and the sequence of events after injury that lead to chronic disease. However, collecting and analyzing these large datasets presents a challenge—such systems are time-consuming to process, and the overwhelming scale of data makes it difficult to parse overall behaviors. This problem calls for an analysis technique that can quickly provide an overview of the groups present in the entire system and also produce meaningful categorization of cell behaviors. Here, we demonstrate the application of an unsupervised method—the Variational Autoencoder (VAE)—to learn the features of cells in cartilage tissue after impact-induced injury and identify meaningful clusters of chondrocyte behavior. This technique quickly generated new insights into the spatial distribution of specific cell behavior phenotypes and connected specific peracute calcium signaling timeseries with long term cellular outcomes, demonstrating the value of the VAE technique. [ABSTRACT FROM AUTHOR]

BACKGROUND: Internal tension-reduction technique is to reconstruct the anterior cruciate ligament through high-strength suture system combined with tendon. It can effectively reduce graft relaxation and frets by sharing the internal load of the knee joint, and has achieved good biomechanical results and clinical efficacy. However, whether it can reduce cartilage degeneration after anterior cruciate ligament reconstruction through stress sharing reduction has not been studied. OBJECTIVE: To investigate the effect of internal tension-reduction technique on articular cartilage degeneration in southern Yunnan small-ear pigs undergoing anterior cruciate ligament reconstruction. METHODS: Ten adult female Yunnan small-ear pigs were selected, and the ipsilateral knee Achilles tendon was taken from the left knee joint for anterior cruciate ligament reconstruction (normal group, n=10), and the ipsilateral knee Achilles tendon from the right knee joint combined with internal tension)reduction and augmentation system for anterior cruciate ligament reconstruction (tension-reduction group, n=10). One year after surgery, the experimental pigs were sacrificed, and the left and right knee cartilage was taken for hematoxylin-eosin staining, Safranin O-fast green staining, Osteoarthritis Research Society International scoring, and immunohistochemistry staining of type II collagen, interleukin-1β, and tumor necrosis factor-alpha in the cartilage. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that in the tension-reduction group, there were mild pathologic changes of osteoarthritis, with a low number of empty bone lacunae and no obvious pathological changes such as fibrosis or cell layer breakage; in the normal group, more severe cartilage damage, with an increased number of empty bone lacunae, loss of chondrocytes near the bone and even the formation of fissures. Safranin O-fast green staining indicated that the tension-reduction group had normal cartilage tissue thickness, flat cartilage surface, a neat cell arrangement in a polar pattern, and no swelling or apoptosis, while in the normal group, the thickness of cartilage tissue was obviously thinner, the cell arrangement was disordered with no polarity, the number of cells was reduced, obvious cartilage fractures and cartilage vacuoles formed, and the absence of cells near the central bone was obvious. The Osteoarthritis Research Society International score was significantly lower in the tension-reduction group than in the normal group (P < 0.05). Immunohistochemical findings showed that the protein expression of type II collagen in cartilage tissue of the tension-reducing group was higher than that of the normal group (P < 0.05), and the protein expression of interleukin 1β and tumor necrosis factor ɑ in cartilage tissue was lower than that of normal group (P < 0.05). To conclude, internal tension-reduction technique can delay the degeneration of articular cartilage in Yunnan small-eared pigs following anterior cruciate ligament reconstruction. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common joint disorder characterized by cartilage degeneration, often leading to pain and functional impairment. Minced cartilage implantation (MCI) has emerged as a promising one-step alternative for large cartilage defects. However, the source of chondrocytes for MCI remains a challenge, particularly in advanced OA, as normal cartilage is scarce. We performed in vitro studies to evaluate the feasibility of MCI using osteophyte cartilage, which is present in patients with advanced OA. Osteophyte and articular cartilage samples were obtained from 22 patients who underwent total knee arthroplasty. Chondrocyte migration and proliferation were assessed using cartilage fragment/atelocollagen composites to compare the characteristics and regenerative potential of osteophytes and articular cartilage. Histological analysis revealed differences in cartilage composition between osteophytes and articular cartilage, with higher expression of type X collagen and increased chondrocyte proliferation in the osteophyte cartilage. Gene expression analysis identified distinct gene expression profiles between osteophytes and articular cartilage; the expression levels of COL2A1, ACAN, and SOX9 were not significantly different. Chondrocytes derived from osteophyte cartilage exhibit enhanced proliferation, and glycosaminoglycan production is increased in both osteophytes and articular cartilage. Osteophyte cartilage may serve as a viable alternative source of MCI for treating large cartilage defects in OA. [ABSTRACT FROM AUTHOR]

Objective: Knee hyperextension is one of the most common compensatory mechanisms in stroke patients. The first aim of the study was to measure knee hyperextension and femoral cartilage thickness in stroke patients. The second aim was to compare the femoral cartilage thickness of the paretic and nonparetic limbs in stroke patients with and without knee hyperextension. Design: Forty stroke patients were included in the study. The patients were divided into two groups according to the presence of knee hyperextension based on kinematic analyses performed during walking with a three-dimensional motion analysis system. The medial femoral cartilage, lateral femoral cartilage, and intercondylar cartilage thicknesses of the paretic and nonparetic sides of the patients were measured by ultrasonography. Results: In the study group, medial femoral cartilage, intercondylar, and lateral femoral cartilage thicknesses were less on the paretic side than on the nonparetic side, while the femoral cartilage thicknesses on the paretic and nonparetic sides were similar in the control group. Paretic side medial femoral cartilage and intercondylar thicknesses were less in the study group compared with the control group, and lateral femoral cartilage thickness was similar between the two groups. Conclusions: Knee hyperextension during walking causes femoral cartilage degeneration in stroke patients. [ABSTRACT FROM AUTHOR]