RESUMO
Mitochondrial dysfunction plays a crucial role in the development of glucocorticoid-induced osteoporosis (GIO). Cytidine monophosphate kinase 2 (Cmpk2), an essential mitochondria-associated gene, promotes the production of free mitochondrial DNA, which leads to the formation of inflammasome-mediated inflammatory factors. However, the specific role of Cmpk2 in GIO remains unclear. In this study, we report that glucocorticoids induce cellular senescence within the bone, particularly in bone marrow mesenchymal stem cells and preosteoblasts. We discovered that glucocorticoids cause mitochondrial dysfunction in preosteoblasts, increasing cellular senescence. Moreover, we observed elevated expression of Cmpk2 in preosteoblasts following glucocorticoid exposure. Inhibiting Cmpk2 expression alleviates glucocorticoid-induced cellular senescence and promotes osteogenic differentiation by improving mitochondrial function. Our study uncovers new mechanisms underlying glucocorticoid-induced senescence in stem cells and preosteoblasts, highlighting the potential of inhibiting the mitochondrial gene Cmpk2 to reduce senescence and enhance osteogenic differentiation. This finding offers a potential therapeutic approach for the treatment of GIO.
Assuntos
Glucocorticoides , Osteoporose , Humanos , Glucocorticoides/efeitos adversos , Osteogênese/genética , Diferenciação Celular/genética , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoblastos/metabolismo , Mitocôndrias/metabolismoRESUMO
Objective: To analyze the effectiveness of minimally invasive safe approach of the knee joint in the treatment of avulsion fractures of the tibial insertion of the posterior cruciate ligament (PCL). Methods: The clinical data of 26 patients with avulsion fractures of tibial insertion of PCL treated with open reduction and internal fixation via minimally invasive safe approach of the knee joint between February 2019 and March 2022 were analyzed retrospectively. There were 18 males and 8 females with an average age of 45.5 years (range, 33-58 years). The causes of injury were traffic accident in 14 cases, falling from height in 7 cases, and sports injury in 5 cases. There were 15 cases of left knee and 11 cases of right knee. The preoperative Lysholm score of knee joint was 34.4±7.3 and the flexion range of motion of knee joint was (69±12)°. According to Meyers classification, there were 8 cases of type â ¡ and 18 cases of type â ¢. The time from injury to operation ranged from 1 to 5 days, with an average of 2 days. Results: The operation time was 40-70 minutes, with an average of 55 minutes; the intraoperative blood loss was 10-30 mL, with an average of 15 mL. Delayed incision healing occurred in 1 case after operation, and the incision healed after conservative treatment, and the incisions of the other patients all healed by first intention. Postoperative X-ray films showed satisfactory fracture reduction. All 26 patients were followed up 3-30 months, with an average of 22 months. No complication such as neurovascular injury, infection, and knee extension disorder occurred after operation. X-ray films at 3 months after operation showed that all fractures healed without displacement of the fracture ends; the posterior drawer test was negative. At last follow-up, the flexion range of motion of knee joint was (120±9)°, the Lysholm score was 90.7±3.8, which were significantly improved when compared with those before operation (t=16.376, P<0.001; t=47.665, P<0.001). Conclusion: The minimally invasive safe approach of the knee joint for the treatment of PCL tibial insertion avulsion fractures is easy to operate, with minimal surgical trauma, safe and reliable approach, and satisfactory recovery of knee joint function after operation.