METTL14 mitigates osteoporosis progression by promoting osteogenic differentiation of BMMSCs through improving mitochondrial dysfunction.

Abstract

Osteoporosis, a prevalent metabolic bone disorder characterized by diminished bone mass and microarchitectural deterioration, poses a significant global health burden. Bone marrow mesenchymal stem cells (BMMSCs) are crucial for bone homeostasis, and their declined osteogenic potential is a key pathogenic factor in osteoporosis. This study investigates the role of METTL14 in BMMSCs, hypothesizing that it attenuates osteoporosis progression by enhancing their osteogenic differentiation. Osteogenic and adipogenic differentiation were assessed by Alizarin Red and Oil Red O staining, respectively. Cell proliferation was evaluated using the CCK-8 assay, and protein expression was analyzed by Western blot. An ovariectomized (OVX) rat model of osteoporosis was established, with bone changes examined through histopathology and immunohistochemistry. Mitochondrial function was assessed via JC-1 staining, ROS/ATP assays, and respiratory chain protein expression analysis. METTL14 upregulation enhanced BMMSC proliferation, promoted osteogenic differentiation, and increased osteogenesis-related protein expression, whereas its suppression had opposing effects. In OVX rats, METTL14 elevation improved bone repair and improved mitochondrial function by recovering membrane potential, reducing mitochondrial ROS, increasing ATP production, and normalizing respiratory chain protein expression. METTL14 mitigates osteoporosis progression by promoting osteogenic differentiation of BMMSCs through improving mitochondrial dysfunction. Our research provides a foundation for targeting METTL14 in osteoporosis treatment.