PurposeThe femoral anteversion angle is considered to be the same as femoral torsion; however, the femoral anteversion angle is strongly inluenced by the femoral posterior condylar morphology. It remains unclear whether the femoral anteversion angle and axial orientation of the femoral trochlea can predict patellar instability. This study aimed to redeine the femoral inherent torsion, verify whether the femoral anteversion angle relects the femoral inherent torsion, and compare the validity and calculate the cut-of values of the femoral anteversion angle and femoral trochlear axial orientation for predicting patellar instability. Methods Seventy-three patients with patellar instability and 73 matched controls underwent computed tomography to measure the femoral anteversion angle, femoral inherent torsion, and femoral trochlear axial orientation. Pearson's product moment correlation coeicients and linear regression were calculated to determine correlations between measurements. Receiver operating characteristic curves and nomograms were plotted to evaluate the predictive validity of the femoral anteversion angle and femoral trochlear axial orientation for patellar instability. Results All measurements showed excellent intra-and inter-observer reliability. Compared with the control group, the patellar instability group had a signiicantly larger femoral anteversion angle (25.4 ± 6.4° vs. 20.2 ± 4.5°) and femoral inherent torsion (18.3 ± 6.7° vs. 15.8 ± 3.4°), and signiicantly smaller femoral trochlear axial orientation (58.1 ± 7.3° vs. 66.9 ± 5.1°). The femoral anteversion angle and femoral trochlear axial orientation had area under the receiver operating characteristic curve values of 79 and 84%, respectively, and cut-of values of 24.5° and 62.7°, respectively. The calibration curve and decision curve analysis showed that the femoral trochlear axial orientation performed better than the femoral anteversion angle in predicting patellar instability. There was a strong correlation between the femoral anteversion angle and femoral inherent torsion (r > 0.8). Linear regression analysis of the femoral inherent torsion with the femoral anteversion angle as the prediction variate showed moderate goodness-of-it (adjusted R 2 = 0.69). ConclusionThe femoral anteversion angle moderately relects the femoral inherent torsion. The femoral trochlear axial orientation is better than the femoral anteversion in predicting patellar instability in terms of predictive eiciency, consistency with reality, and net clinical beneit. These indings warn orthopaedists against overstating the role of the femoral anteversion angle in patellar instability, and suggest that the femoral trochlear axial orientation could aid in identifying at-risk patients and developing surgical strategies for patellar instability. Level of evidence III. KeywordsPatellar instability • Femoral anteversion • Femoral inherent torsion • Axial orientation of the femoral trochlea * Fei Wang

Patellar instability (PI) is a common knee injury in adolescents, but the crucial biomarkers and molecular mechanisms associated with it remain unclear. We established a PI mouse model and investigated PI-related changes in gene expression by RNA sequencing (RNA-seq). Differentially expressed gene (DEG) analysis and enrichment analysis were performed to identify crucial genes and pathways associated with PI. Subsequently, a protein-protein interaction, DEG-miRNA, DEG-transcription factors, and DEG-drug interaction networks were constructed to reveal hub genes, molecular mechanism, and potential drugs for PI. Finally, the reliability of the sequencing results was confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Upon comparison with the control group, 69 genes were differently expressed in PI, including 17 upregulated and 52 downregulated ones. The DEGs were significantly enriched in Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and immune responses. The protein–protein interaction network identified ten PI-related hub genes, all of which are involved in the JAK/STAT signaling pathway or inflammation-related pathways. DEG-miRNA and DEG-transcription factor networks offered new insights for regulating DEGs post-transcriptionally. We also determined potential therapeutic drugs or molecular compounds that could restore dysregulated expression of DEGs via the DGIdb database. RT-qPCR results were consistent with the RNA-seq, confirming the reliability of the sequencing data. Immunohistochemistry results suggested that JAK1 and STAT3 expression was increased in PI. Our study explored the potential molecular mechanisms in PI, provided promising biomarkers and suggested a molecular basis for therapeutic targets for this condition.

Background: Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease among the aged population. However, current treatments for OA are limited to alleviating symptoms, with no therapies that prevent and regenerate cartilage deterioration. Purpose: To assess the effects of platelet-derived exosomes (Plt-exos) on OA and then to explore the potential molecular mechanism. Study Design: Controlled laboratory study. Methods: Exosomes derived from human apheresis platelets were isolated and identified. The effects of Plt-exos in protecting chondrocytes under interleukin 1β stimulation were evaluated by analyzing the proliferation and migration in human primary chondrocytes. RNA sequencing was later performed in vitro for primary chondrocytes to reveal the underlying mechanisms of Plt-exo treatment. Anterior cruciate ligament transection was used to construct an OA mice model, and intra-articular injection of Plt-exos was given once a week for 6 weeks. Mice were sacrificed 4 weeks after the last injection. Histologic and immunohistochemistry staining and micro–computed tomography analysis were performed to assess alterations of articular cartilage and subchondral bone. Results: Plt-exos significantly promoted proliferation and migration of chondrocytes within a dose-dependent manner, as well as dramatically promoted cartilage regeneration and attenuated abnormal tibial subchondral bone remodeling, thus slowing the progression of OA. After being treated with Plt-exos, 1797 genes were differentially expressed in chondrocytes (923 upregulated and 874 downregulated genes). Functional enrichment results and hub genes were mainly involved in anti-inflammatory effects, mediating cell adhesion, stimulating cartilage repair, promoting anabolism, and inhibiting catabolism. Conclusion: Our results demonstrated that Plt-exos promoted chondrocyte proliferation and migration in vitro, as well as attenuated cartilage degeneration, improved the microarchitecture of subchondral bone, and retarded OA progression in vivo. Clinical Relevance: Our study illustrated that the administered Plt-exos could alleviate knee OA by attenuating cartilage degeneration and subchondral bone loss, possibly serving as a novel promising treatment for OA in the future.