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Purpose Methods Results Conclusion Level of Evidence This study aimed to compare in vivo kinematics during weight‐bearing daily activities and determine the relationship with clinical outcomes in patients undergoing total knee arthroplasty (TKA) with a medial‐pivot (MP, Evolution™) versus a posterior‐stabilized (PS, Persona®) design under constant conditions of intraoperative soft tissue balance.Forty patients undergoing MP or PS‐TKA under similar conditions of soft tissue balance were enrolled in this prospective randomized controlled trial. Outcome measures included clinical knee society scores (KSS) and knee injury and osteoarthritis outcome scores (KOOS). A kinematic assessment was conducted while the participants performed lunge and step‐up activities under fluoroscopic guidance.Eighteen patients in each arm completed 1‐year follow‐up and were included in the analysis. All patients experienced pain relief and satisfactory knee function postoperatively. In kinematics, in the MP arm, the medial femoral condyle remained consistent, whereas the lateral femoral condyle gradually shifted posteriorly with increasing knee flexion. Conversely, in the PS arm, paradoxical anterior movement of the medial femoral condyle accompanied the lateral pivot motion. During lunge and step‐up activities, a medial‐pivot motion was observed in 83% and 72% of knees in the MP arm, respectively, compared with 22% and 11% in the PS arm. Despite these differences in kinematics, there were no statistically significant differences in the KSS and KOOS between the two groups.Under weight‐bearing conditions during flexion, knees that underwent Evolution™ MP‐TKA did not show superior clinical results compared to Persona® PS‐TKA, despite exhibiting in vivo kinematics closely resembling the normal in vivo pattern.Therapeutic studies—Level I. [ABSTRACT FROM AUTHOR]

Introduction: Slight lateral laxity exists in normal knee especially in flexion. The lateral laxity in flexion has possibility to affect the outcome after total knee arthroplasty (TKA). Purpose: The purpose of this study was to determine how intraoperative laxity in flexion affects patient-reported outcome after total knee arthroplasty. Methods: We retrospectively analysed 98 knees with osteoarthritis that underwent total knee arthroplasty. After bone resection, ligament imbalance and joint component gaps were measured using an offset-type tensor while applying a 40-lb joint distraction force at 0° and 90° of knee flexion. The lateral laxity in flexion was determined by subtracting polyethylene insert thickness from the lateral gap at 90°. All patients were divided into three groups: ≤ 2 mm (A), 2–5 mm (B), and > 5 mm (C). One year after surgery, patients were asked to fill out questionnaires using the new Knee Society Score after examination outside the consultation room. Results: The mean intraoperative lateral laxities at 90° were − 0.2 ± 2.1 mm, 3.5 ± 0.7 mm, and 6.7 ± 1.9 mm in groups A, B, and C, respectively. The symptom score of group C was significantly lower than those of groups A or B. There were no significant differences in terms of satisfaction or the expectation and activity scores among all groups. There were no significant differences in terms of alignment after total knee arthroplasty among all groups. Conclusions: Excessive lateral laxity possibly resulted in worse patient-reported outcomes. However, slight lateral laxity of 2–5 mm might have no effect on patient-reported outcome and this slight varus imbalance could be acceptable. Altogether, our findings would lead to avoidance of excessive medial release in soft tissue balancing. [ABSTRACT FROM AUTHOR]

Germinal center-associated nuclear protein (GANP) is a 210-kDa protein that is upregulated in rapidly proliferating B cells. GANP contains regions for RNA-primase and minichromosome maintenance 3 (MCM3)-associated activities, as well as a Sac3-homology region, which is associated with mRNA export in yeast. Here, we examined the role of GANP in mRNA export and cell proliferation in mammalian cells. The ganp small interfering RNA (siRNA) induced cell-cycle arrest at the G2/M-phase, but increased abnormal chromosome alignment of metaphase chromosomes and cell apoptosis in HeLa cells. These changes were not associated with either the abnormality of the spindle assembly checkpoint or the expression level of cohesin. ganp siRNA disrupted the assembly and localization of cohesin at the centromeres in metaphase cells, which is a quite similar phenotype caused by Shugoshin-1 (Sgo1) siRNA-treatment, which was reported previously. ganp siRNA did induce a selective decrease in Sgo1 transcript levels in the cytoplasm, resulting in a lack of cohesin at the centromeres in metaphase and premature separation of the sister chromatids at mitosis. GANP lacking the Sac3-homology region caused the dominant-negative effect with similar abnormalities and impaired mRNA export. Thus, human GANP is critically involved in cell proliferation at the mitotic phase through its selective support of Sgo1 mRNA export. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor (FGF)–2 has the potential to enhance tendon-to-bone healing after rotator cuff (RC) injury. Hypothesis: FGF-2 stimulates tenogenic differentiation of progenitors to improve the biomechanical strength and histological appearance of repaired RCs in rats. Study Design: Controlled laboratory study. Methods: Adult male Sprague-Dawley rats (N = 156) underwent unilateral surgery to repair the supraspinatus tendon to insertion sites. The FGF-2-treated group (gelatin hydrogel containing 5 μg of FGF-2) and a control group (gelatin hydrogel only) were compared to investigate the effects of FGF-2 at 2, 4, 6, 8, and 12 weeks postoperatively. Biomechanical testing was performed at 6 and 12 weeks. Semiquantitative histological analysis and immunohistochemical analysis for the proliferating cell nuclear antigen (PCNA) were performed, and the expression of tendon-related markers, including Scleraxis (Scx) and Tenomodulin (Tnmd), was monitored by real-time reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization. SRY-box containing gene 9 (Sox9) expression was monitored by RT-PCR and immunohistochemical analysis. At 2 and 4 weeks, immunohistochemical analysis for mesenchymal stem cell (MSC) markers was also performed. Results: The FGF-2-treated group demonstrated a significant improvement in mechanical strength at 6 and 12 weeks and significantly higher histological scores than the control group at ≥4 weeks. The average incidence of PCNA-positive cells was significantly higher at 2 and 4 weeks, and more cells expressing MSC markers were detected at the insertion site in the FGF-2-treated group. The expression level of Scx increased significantly in the FGF-2-treated group from 4 to 8 weeks, while the Tnmd level increased significantly from 4 to 12 weeks postoperatively. The localization of Tnmd overlapped with the locations of reparative tissues accompanying collagen fibers with an aligned orientation. Sox9 expression was significantly upregulated at 4 weeks in the FGF-2-treated group. Conclusion: FGF-2 promotes growth of the tenogenic progenitor cells, which participate in tendon-to-bone healing, resulting in biomechanical and histological improvement of the repaired RC. Clinical Relevance: These findings provide clues regarding the clinical development of regenerative repair strategies for RC injury. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the association between the T 1 ρ and T 2 values and the progression of cartilage degeneration in patients of the same age group. Materials and methods Sagittal T 1 ρ and T 2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T 1 ρ and T 2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T 1 ρ and T 2 values and the degree of patella cartilage degeneration. Results There were no significant differences in age among the four groups. Both the T 1 ρ and T 2 values showed a positive correlation with the degree of OA progression ( ρ = 0.737 and ρ = 0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T 1 ρ mapping, but not in the T 2 mapping. Conclusions Our study confirmed that T 1 ρ and T 2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group. [ABSTRACT FROM AUTHOR]

The article presents a study on articular cartilage degeneration which can develop after anterior cruciate ligament reconstruction (ACLR). It focuses on risk factors in the early postoperative period. The T1ρ spin-lattice relaxation in the rotating frame magnetic resonance imaging is described. The baseline T1ρ value of the medial femoral condyle (MFC) and lateral FC (LFC) was higher in patients with cartilage lesions.

Abstract: We performed an in vivo radiographic analysis of tibiofemoral and polyethylene (PE) insert motions during weight-bearing kneeling beyond 120° of flexion in one high-flexion knee arthroplasty design to determine if kinematics changed over time and if axial rotation occur between the PE insert and the tibial baseplate. Twenty knees implanted with a posterior-stabilized rotating-platform (RP) knee arthroplasty were postoperatively evaluated at 3, 6, and 12months. The averaged flexion angles were 122°, 129°, and 131° at 3, 6, and 12months, respectively, showing that the improvement of flexion was achieved up to 6months. The femoral condyles translated posteriorly from extension to maximum flexion. There was a significant increase in AP translation of femoral lateral condyle in the maximum flexion kneeling between 12months and the two other intervals (p=0.0003 at 3months and p=0.016 at 6months), while no differences in those of medial condyle between all intervals. Almost all rotation occurred at the surface between the tibial baseplate and the PE insert (p=0.0479 at 3months, p=0.0008 at 6months, and p=0.0479 at 12months), almost no rotation occurred at the surface between the PE insert and the femoral component. There were significant increases in the amount of internal rotation angle during full flexion between the tibial component and the PE insert up to 12months. Knees implanted with this RP knee arthroplasty design show deep-flexion knee kinematics that are consistent with the implant design intent. [Copyright &y& Elsevier]

Human mesenchymal stem/stromal cells (hMSCs), when engrafted into immunodeficient mice, can form ectopic bone organs with hematopoietic stem cell (HSC) supportive functions. However, the ability to do so, through a cartilage intermediate, appears limited to 30% of donor bone marrow samples. In this study, we characterize the heterogeneous nature of hMSCs and their ability to efficiently form humanized ossicles observed in "good donors" to correlate with the frequency and functionality of chondrocyte progenitors. Flow cytometry of putative hMSC markers was enriched in the CD271+CD51+ stromal cell subset, which also possessed enhanced hMSC activity as assessed by single-cell colony-forming unit fibroblast (CFU-F) and undifferentiated mesensphere formation. Transcriptome analysis of CD271+ cells presented upregulation of chondrogenesis-/osteogenesis-related genes and HSC/niche maintenance factors such as C-X-C motif chemokine 12 (CXCL12) and ANGIOPOIETIN 1. Among the candidate genes selected to enrich for subsets with greater chondrogenic ability, cells negative for the actin cross-linker PALLADIN displayed the greatest CFU-F potential. Our study contributes to a better characterization of ossicle-forming hMSCs and their efficient isolation for the optimized engineering of human bone organs. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor β1 (TGF-β1) positively regulates the tenogenic marker genes scleraxis (Scx) and tenomodulin (Tnmd) in mesenchymal progenitors in vitro. However, little is known about the effect of TGF-β1 on the expression of tenogenic markers during rotator cuff (RC) healing in rats. Hypothesis: TGF-β1 improves the biomechanical properties and histological maturity of reparative tissue in a rat RC repair model by stimulating the growth of tenogenic cells. Study Design: Controlled laboratory study. Methods: Adult male Sprague-Dawley rats (N = 180) underwent unilateral supraspinatus tendon-to-bone surgical repair and were randomly treated with a gelatin hydrogel presoaked in TGF-β1 (100 ng) or phosphate-buffered saline. The effects of TGF-β1 on RC healing were investigated at 2, 4, 6, 8, and 12 weeks postoperatively by immunostaining for proliferating cell nuclear antigen, by real-time reverse transcription polymerase chain reaction and in situ hybridization or immunostaining for enthesis-related markers (SRY-box containing gene 9 [Sox9], Scx, and Tnmd), and by real-time reverse transcription polymerase chain reaction and immunostaining for type I and III collagen. At 6 and 12 weeks postoperatively, biomechanical testing, micro–computed tomography, and biochemical analysis were also performed. At 2 and 4 weeks postoperatively, mesenchymal stem cell–related markers, phospho-Smad2, and matrix metalloproteinase 9 (MMP-9) and MMP-13 were assessed by immunostaining. Results: The TGF-β1-treated group had significantly higher ultimate load to failure and tissue volume at 6 and 12 weeks postoperatively and a higher collagen content at 12 weeks compared with the saline group. Tendon-related gene expression, histological maturity, cell proliferation, and mesenchymal stem cell–related marker immunoreactivity were not affected by exogenously administrated TGF-β1 at all time points. In the TGF-β1-treated group, the percentage of phospho-Smad2-positive cells within the healing tissue increased, whereas the expression of MMP-9 and MMP-13 significantly decreased at 2 and 4 weeks postoperatively. Conclusion: TGF-β1 enhances formation of tough fibrous tissues at the healing site by inhibiting MMP-9 and MMP-13 expression to increase collagen accumulation but without the growth of tenogenic lineage cells. Clinical Relevance: These findings suggest that TGF-β1 could be used for enhancing biomechanical strength after RC surgical repair. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The purpose of this study was to clarify the detectability of the International Cartilage Repair Society (ICRS) grade 1 cartilage lesions in anterior cruciate ligament (ACL)–injured knees using T1ρ and T2 mapping. Materials and Methods: We performed preoperative T1ρ and T2 mapping and 3D gradient–echo with water–selective excitation (WATS) sequences on 37 subjects with ACL injuries. We determined the detectability on 3D WATS based on arthroscopic findings. The T1ρ and T2 values (ms) were measured in the regions of interest that were placed on the weight–bearing cartilage of the femoral condyle. The receiver operating characteristic (ROC) curve based on these values was constructed using the arthroscopic findings as a reference standard. The evaluation of cartilage was carried out only in the weight–bearing cartilage. The cut–off values for determining the presence of a cartilage injury were determined using each ROC curve, and the detectability was calculated for the T1ρ and T2 mapping. Results: The cut–off values for the T1ρ and T2 were 41.6 and 41.2, respectively. The sensitivity and specificity of T1ρ were 91.2% and 89.5%, respectively, while those of T2 were 76.5% and 81.6%, respectively. For the 3D WATS images, the same values were 58.8% and 78.9%, respectively. Conclusions: Our study demonstrated that the T1ρ and T2 values were significantly higher for ICRS grade 1 cartilage lesions than for normal cartilage and that the two mappings were able to non–invasively detect ICRS grade 1 cartilage lesions in the ACL–injured knee with a higher detectability than were 3D WATS images. [Copyright &y& Elsevier]

Mammalian cells attempt to maintain their homeostasis under endoplasmic reticulum ( ER) stress. If the stress cannot be alleviated, cells are led to apoptosis through induction of C/ EBP homologous protein ( CHOP). ER stress is provoked in osteoarthritis chondrocytes, and intracellular accumulation of advanced glycation end products ( AGEs) in chondrocytes is a possible cause. To clarify the role of intracellular AGE accumulation in chondrocytes, the present study investigated the effect of intracellular AGE accumulation on ER stress and apoptosis by in vitro and in vivo analysis. Intracellular AGE accumulation induced by AGE precursors caused apoptosis, induced expression of ER stress markers, and led to co-localization of AGEs with glucose-regulated protein 78, leading to formation of high-molecular-weight complexes in cultured chondrocytes. These reactions were inhibited by an AGE formation inhibitor. CHOP deletion inhibited apoptosis induced by intracellular AGE accumulation. In vivo intracellular AGE accumulation induced by intra-articular injection of AGE precursors caused ER stress and apoptosis in chondrocytes and led to degradation of articular cartilage. Additionally, intracellular AGE accumulation increased the degree of cartilage degradation in an osteoarthritis model. These data indicate that intracellular accumulation of AGEs induces modification of unfolded protein response-related protein by AGEs and apoptosis via ER stress in chondrocytes. Moreover, the in vivo study showed that intracellular AGE accumulation in chondrocytes is involved in the occurrence and progression of osteoarthritis through ER stress. Thus, research on mechanisms of apoptosis via ER stress induced by intracellular AGE accumulation in chondrocytes will lead to a new understanding of osteoarthritis pathology. [ABSTRACT FROM AUTHOR]

Abstract: Advanced glycation end products (AGEs) may be associated with osteoarthritis (OA), because the accumulation of AGEs in articular cartilage are among the most striking age-related changes. AGEs modify the tissue protein structure and function and stimulate the cellular responses mediated by a specific receptor for AGEs (RAGE). This study investigated the localization of AGEs in degenerated cartilage using newly identified epitope-specific antibodies to determine the linkage between the distribution of AGEs and the development and progression of OA. Osteochondral specimens of the tibial plateau from OA patients were immunostained by specific antibodies against N ɛ-(carboxymethyl)lysine (CML), N ɛ-(carboxyethyl)lysine (CEL), pentosidine, GA-pyridine, and RAGE. The immunohistochemical distribution of these epitopes was evaluated during cartilage degeneration. The immunoreactivity (IR) of AGEs and RAGE was stronger in cells rather than in the extracellular matrix. Higher IR of cellular CML and CEL was observed in both mild and severe OA cartilage in comparison to macroscopically intact cartilage. There was a strong association between GA-pyridine and RAGE in the pattern of increasing IR with the OA grade. These IR patterns of AGEs varying with cartilage degeneration indicate that AGE modified proteins are associated with cartilage degeneration. The coincidental up-regulation of GA-pyridine and RAGE suggests that GA-pyridine is the most significant AGE for cartilage degeneration via the RAGE pathway. [Copyright &y& Elsevier]