Melatonin suppresses bone marrow adiposity in ovariectomized rats by rescuing the imbalance between osteogenesis and adipogenesis through SIRT1 activation

• DOI: 10.1016/j.jot.2022.10.002
• Publication Date: 2022-10-27T05:16:14Z
• Authors: Xiaoxiong Huang; Weikai Chen; Chao Gu; Hao Liu; Mingzhuang Hou; Wanjin Qin; Xuesong Zhu; Xi Chen; Tao Liu; Huilin Yang; Fan He
• Keywords: 0301 basic medicine; 03 medical and health sciences; Adipogenesis; SIRT1; RC925-935; Osteogenesis; Marrow adiposity; Original Article; Diseases of the musculoskeletal system; Bone marrow-derived mesenchymal stem cells; Melatonin

Accelerated imbalance between bone formation and resorption is associated with loss in postmenopausal osteoporosis. Studies have shown that this accompanied by an increase marrow adiposity. Melatonin was to improve impaired capacity of marrow-derived mesenchymal stem cells from ovariectomized rats (OVX-BMMSCs).To investigate whether the anti-osteoporosis effect melatonin involves regulation equilibrium osteogenic adipogenic differentiation osteoporotic BMMSCs.To induce osteoporosis, female Sprague-Dawley received ovariectomy (OVX). Primary BMMSCs were isolated tibiae femurs OVX sham-op induced towards or differentiation. Matrix mineralization determined Alizarin Red S (ARS) lipid evaluated Oil O. injected through tail vein. Bone microarchitecture using micro computed tomography adiposity examined histology staining.OVX-BMMSCs exhibited a compromised potential enhanced lineage adipocytes. In vitro improved OVX-BMMSCs promoted matrix enhancing expression transcription factor RUNX2 dose-dependent manner. Moreover, significantly inhibited suppressed adipogenesis down-regulating peroxisome proliferator-activated receptor γ (PPARγ). Intravenous injection prevented mass reduction architecture destruction rats. Importantly, there significant inhibition adipose tissue marrow. Mechanistic investigations revealed SIRT1 involved melatonin-mediated determination cell fate. Inhibition abolished protective effects on inducing adipocyte differentiation.Melatonin reversed switch osteogenesis activating signaling pathway. Restoration commitment over-accumulation protected osteoporosis.Determination fate osteoblasts adipocytes plays pivotal role regulating metabolism. This study demonstrates estrogen-deficient suppressing accumulation may serve as promising candidate for treatment osteoporosis clinics.