Gubi decoction mitigates knee osteoarthritis via promoting chondrocyte autophagy through METTL3-mediated ATG7 m6A methylation.

Knee osteoarthritis (KOA) is a chronic joint disease that significantly affects the health of the elderly. As an herbal remedy, Gubi decoction (GBD) has been traditionally used for the treatment of osteoarthritis-related syndromes. However, the anti-KOA efficacy and mechanism of GBD remain unclear. This study aimed to experimentally investigate the anti-KOA efficacy and the underlying mechanism of GBD. The medial meniscus (DMM) mice model and IL-1ß-stimulated chondrocytes were, respectively, constructed as in vivo and in vitro models of KOA to evaluate the osteoprotective effect and molecular mechanism of GBD. The UPLC-MS/MS analysis showed that GBD mainly contained pinoresinol diglucoside, rehmannioside D, hesperidin, liquiritin, baohuoside I, glycyrrhizic acid, kaempferol and tangeretin. Animal experiment showed that GBD could alleviate articular cartilage destruction and recover histopathological alterations in DMM mice. In addition, GBD inhibited chondrocyte apoptosis and restored DMM-induced dysregulated autophagy evidenced by the upregulation of ATG7 and LC3 II/LC3 I but decreased P62 level. Mechanistically, METTL3-mediated m6A modification decreased the expression of ATG7 in DMM mice, as it could be significantly attenuated by GBD. METTL3 overexpression significantly counteracted the protective effect of GBD on chondrocyte autophagy. Further research showed that GBD promoted proteasome-mediated ubiquitination degradation of METLL3. Our findings suggest that GBD could act as a protective agent against KOA. The protective effect of GBD may result from its promotion on chondrocyte autophagy by suppressing METTL3-dependent ATG7 m6A methylation.

Arthroscopic rotator cuff repair combined with platelet-rich plasma products can reduce the rate of retearing and improve clinical outcomes: A meta-analysis of randomized controlled trials.

BACKGROUND: Although several studies on the potential benefits of protein-rich plasma (PRP) therapy for rotator cuff injuries have been published, the results have been conflicting. Therefore, this study aimed to determine whether PRP is beneficial for the prevention of retears after arthroscopic rotator cuff repair (ARCR). METHODS: Two reviewers conducted independent literature searches based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials (RCTs) comparing a PRP treatment group with a control group were included. The quality of evidence was assessed using the Cochrane Collaboration Risk of Bias Tool. Clinical outcomes were compared using the risk ratio (RR) for dichotomous variables and weighted mean difference (WMD) for continuous variables. Statistical significance was set at P < .05. RESULTS: This review included 21 RCTs (1359 patients). Significant results were noted in favor of PRP treatment compared with controls based on retearing rates (16.5% vs 23.6%, respectively; P = .002) and the Constant score in the short term (WMD: 1.98; 95% confidence interval [CI], 0.27-3.70; I2 = 0%; P = .02), medium term and long term (WMD: 2.56 [95% CI: 1.57-3.55]; I2 = 2%; P < .001); the University of California, Los Angeles score in the short term (WMD: 1.14 [95% CI: 0.43-1.85]; I2 = 25%; P = .002) but not in the medium and long term (WMD: 0.66 [95% CI: -0.16 to 1.48]; I2 = 57%; P = .11); and the visual analog scale score in the short term (WMD: -0.63 [95% CI: -0.83 to-0.43]; I2 = 41%; P < .001), medium and long term (WMD: -0.12 [95% CI: -0.19 to-0.05]; I2 = 0%; P = .008). There was no significant difference in American Shoulder and Elbow Surgeons scores between the treatment and control groups in the short term (WMD: -0.48 [95% CI: -2.80 to 1.85]; I2 = 22%; P = .69) or medium and long term (WMD: 0.92 [95% CI: -1.56 to 3.39]; I2 = 40%; P = .47). CONCLUSION: Intraoperative use of PRP reduces the risk of rotator cuff repair failure, improves clinical outcomes, and reduces recurrence rates.