BMC Musculoskeletal Disorders最新文献

Background: Intervertebral disc degeneration (IVDD) is the primary pathological driver of chronic low back pain. While the mechanical role of skeletal muscle in spinal stability is well-established, its paracrine influence on IVDD-specifically via exosomes-remains poorly understood. This study investigated whether senescent skeletal muscle cell-derived exosomes (sSkM-Exos) aggravate metabolic dysregulation in nucleus pulposus cells (NPCs) and explored the underlying molecular mechanisms.

Methods: Senescence was induced in skeletal muscle cells (SkMCs) using hydrogen peroxide (H₂O₂), and sSkM-Exos were isolated via differential centrifugation and characterized. The internalization of sSkM-Exos by NPCs was observed. In vitro, the effects of sSkM-Exos on NPCs proliferation, senescence, apoptosis, and extracellular matrix (ECM) metabolism (COL2, ACAN, MMP13, and ADAMTS5) were evaluated. The involvement of the p38MAPK pathway was assessed using the inhibitor SB203580. In vivo, the impact of sSkM-Exos was validated using a rat IVDD model, monitored by disc height, MRI T2-weighted signaling, and histological analysis.

Results: We induced senescent skeletal muscle cells (SkMCs) with hydrogen peroxide (H₂O₂), extracted and identified sSkM-Exos via differential centrifugation. Our findings demonstrate that sSkM-Exos can be internalized by NPCs. In vitro, sSkM-Exos enhanced H₂O₂-induced NPC proliferation inhibition, senescence, apoptosis, and extracellular matrix (ECM) imbalance (downregulated COL2/ACAN, upregulated MMP13/ADAMTS5). Mechanistically, these effects were associated with p38MAPK activation; the p38MAPK inhibitor SB203580 partially reversed these impairments. In vivo, local sSkM-Exos injection was observed to exacerbate disc height loss and histological degeneration in a rat IVDD model.

Conclusions: In conclusion, sSkM-Exos were found to contribute to NPC senescence and ECM imbalance, likely through the activation of the p38MAPK pathway. These findings propose a cross-tissue regulatory network that supplements the traditional biomechanical model with a molecular perspective under experimental conditions. This study offers a new dimension to our understanding of IVDD pathogenesis and suggests that targeting sSkM-Exos or the p38MAPK pathway may hold promise as a therapeutic strategy to mitigate IVDD.

Purpose: A greater hindfoot valgus angle is potentially associated with worse outcomes after talocalcaneal coalition (TCC) resection. However, the impact of concomitant flatfoot on TCC resection outcomes remains controversial. The aim of this study was to discuss the effect of flatfoot on the outcomes of isolated TCC resection.

Methods: A retrospective analysis was conducted on patients who underwent isolated resection for symptomatic TCC between 2016 and 2024. Patients were divided into flatfoot (FF, n = 20) and non-flatfoot groups (NF, n = 25) based on the diagnostic criteria for radiographic flatfoot on preoperative weightbearing radiographs: Meary's angle (MA) > 4°, calcaneal pitch (CP) < 18°, talonavicular coverage angle (TNCA) > 7° and Kite's angle (KA) > 40°. Preoperative and postoperative visual analogue scale (VAS) scores and American Orthopaedic Foot & Ankle Society (AOFAS) scores were used to evaluate functional outcomes, whereas flatfoot-related angles (CP, MA, TNCA and KA) were measured to assess radiographic outcomes.

Results: Forty-four patients (45 feet) were included in this study. The mean age at the time of surgery was 26.7 ± 6.6 years. All cases included were non-osseous coalitions. Twenty feet were in the FF group, and 25 feet were in the NF group. All patients were followed up for 50.6 ± 18.0 months. At the final follow-up, the VAS score was 1.3 ± 0.8, and the AOFAS score was 83.9 ± 9.0 in the FF group. In the NF group, the VAS score was 1.5 ± 0.9, and the AOFAS ankle-hindfoot score was 83.3 ± 6.6. Both groups demonstrated statistically significant improvements in functional outcomes (VAS and AOFAS) compared to preoperative values (p < 0.05). No significant differences in the radiographic measurements of flatfoot were noted between the two groups at the final follow-up.

Conclusion: Isolated resection is effective for treating symptomatic TCC. Concomitant mild flatfoot did not adversely affect outcomes, suggesting that resection is a viable option for TCC patients with combined flatfoot.