Emerging evidence suggests that osteoarthritis is associated with high cholesterol levels in some osteoarthritis patients. However, the specific mechanism under this metabolic osteoarthritis phenotype remains unclear. We find that cholesterol metabolism-related gene, LRP3 (low-density lipoprotein receptor-related protein 3) is significantly reduced in high-cholesterol diet mouse’s cartilage. By using Lrp3−/− mice in vivo and LRP3 lentiviral-transduced chondrocytes in vitro, we identify that LRP3 positively regulate chondrocyte extracellular matrix metabolism, and its deficiency aggravate the degeneration of cartilage. Regardless of diet, LRP3 overexpression in cartilage attenuate anterior cruciate ligament transection induced osteoarthritis progression in rats and Lrp3 knockout-induced osteoarthritis progression in mice. LRP3 knockdown upregulate syndecan-4 by activating the Ras signaling pathway. We identify syndecan-4 as a downstream molecular target of LRP3 in osteoarthritis pathogenesis. These findings suggest that cholesterol-LRP3- syndecan-4 axis plays critical roles in osteoarthritis development, and LRP3 gene therapy may provide a therapeutic regimen for osteoarthritis treatment.

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Background To evaluate the anatomic geometry of the posterior intercondylar eminence and its association with PCL injury risk. Methods Patients who underwent primary PCL reconstruction from 2015 to 2018 were retrospectively analyzed. The control group included inpatients diagnosed with ACL rupture because of a sports-related accident during the same period, matched by age, gender, height, weight, and side of injury. Measurements of the height of the apex of the posterior intercondylar eminence (HPIE), the slope length (SLPIE) and the slope angle (SAPIE) of the posterior intercondylar eminence were performed using conventional MRI scans assessed by 2 blinded, independent raters. Intraclass correlation coefficients (ICCs) was used to evaluate the consistency of measurement results. Independent sample t tests, Chi-square tests, and logistic analyses were used to compare the two group, with P < 0.05 considered statistically significant. Results Fifty-five patients with PCL rupture met the inclusion criteria and 55 PCL-intact matched controls were included. There were no significant differences between the groups in gender (P = 1.000), limb side (P = 0.848), age (P = 0.291), BMI (P = 0.444) or height (P = 0.290). Inter-observer reproducibility was excellent agreement in HPIE, SLPIE and SAPIE of case and control groups (ICC: HPIE = 0.81, SLPIE = 0.77, SAPIE = 0.85). Patients with PCL rupture had significantly greater HPIE, SAPIE (both P < 0.001), and SLPIE (P < 0.05) than PCL-intact patients. The multivariable analysis showed that HPIE (OR, 1.62 [95% CI, 1.24–2.11], P < 0.001) and SAPIE (OR, 1.17 [95% CI, 1.05–1.31], P < 0.001) were independent factors associated with PCL rupture. Conclusion Through this retrospective observational study, we found that patients with PCL rupture may have a higher posterior intercondylar eminence compared to PCL-intact patients. Level of evidence III.