miR-613 regulates osteogenic differentiation by targeting TIMP3 in postmenopausal osteoporosis
摘要
Osteoporosis is a metabolic bone disease prevalent in postmenopausal women due to estrogen deficiency, leading to impaired bone homeostasis. Bone marrow mesenchymal stem cells (BMSCs) play a crucial role in bone formation and microRNA-613 (miR-613) has been implicated in bone metabolism, but its role in osteoporosis remains unclear. This study explores the expression of miR-613 in postmenopausal osteoporosis (PMOP) and its diagnostic value.
MethodsmiR-613 levels in 84 PMOP patients and 71 healthy controls were analyzed by qRT-PCR. Receiver operating characteristic (ROC) curve analysis was used to assess its diagnostic potential. In vitro, hBMSCs were induced to differentiate into osteoblasts by β-glycerophosphate and miR-613 inhibition was used to evaluate its role in osteogenesis, cell proliferation, apoptosis, and osteogenic marker expression. The interaction between miR-613 and TIMP3 was confirmed using dual-luciferase assays.
ResultsmiR-613 expression was significantly lower in PMOP patients compared to healthy controls (P < 0.0001), and ROC analysis showed its potential as a diagnostic biomarker (AUC = 0.843, 95% CI = 0.783–0.904). Inhibition of miR-613 suppressed osteogenic differentiation, decreased cell proliferation, and increased apoptosis. TIMP3 was identified as a direct target of miR-613 and its expression inversely correlated with miR-613 levels in PMOP patients. Silencing TIMP3 partially reversed the suppressive effects of miR-613 inhibition on osteogenesis.
ConclusionmiR-613 promotes osteogenic differentiation of BMSCs by targeting TIMP3. Its downregulation in PMOP patients points to its potential as a diagnostic biomarker and therapeutic target.