Details

Autor(en) / Beteiligte

• Xie, Yan
• Zhou, Jie
• Tian, Lijie
• Dong, Yuan
• Yuan, Hairui
• Zhu, Endong
• Li, Xiaoxia
• Wang, Baoli

Titel

miR‐196b‐5p Regulates Osteoblast and Osteoclast Differentiation and Bone Homeostasis by Targeting SEMA3A

Ist Teil von

• Journal of bone and mineral research, 2023-08, Vol.38 (8), p.1175-1191

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• ABSTRACT miR‐196b‐5p plays a role in various malignancies. We have recently reported its function in regulating adipogenesis. However, it remains to be clarified whether and how miR‐196b‐5p affects bone cells and bone homeostasis. In this study, in vitro functional experiments showed an inhibitory effect of miR‐196b‐5p on osteoblast differentiation. Mechanistic explorations revealed that miR‐196b‐5p directly targeted semaphorin 3a (Sema3a) and inhibited Wnt/β‐catenin signaling. SEMA3A attenuated the impaired osteogenesis induced by miR‐196b‐5p. Osteoblast‐specific miR‐196b transgenic mice showed significant reduction of bone mass. Trabecular osteoblasts were reduced and bone formation was suppressed, whereas osteoclasts, marrow adipocytes, and serum levels of bone resorption markers were increased in the transgenic mice. The osteoblastic progenitor cells from the transgenic mice had decreased SEMA3A levels and exhibited retarded osteogenic differentiation, whereas those marrow osteoclastic progenitors exhibited enhanced osteoclastogenic differentiation. miR‐196b‐5p and SEMA3A oppositely regulated the expression of receptor activator of nuclear factor‐κB ligand and osteoprotegerin. The calvarial osteoblastic cells expressing the transgene promoted osteoclastogenesis, whereas the osteoblasts overexpressing Sema3a inhibited it. Finally, in vivo transfection of miR‐196b‐5p inhibitor to the marrow reduced ovariectomy‐induced bone loss in mice. Our study has identified that miR‐196b‐5p plays a key role in osteoblast and osteoclast differentiation and regulates bone homeostasis. Inhibition of miR‐196b‐5p may be beneficial for amelioration of osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR). This study has identified miR‐196b‐5p as a key modulator of osteoblast and osteoclast differentiation and bone homeostasis. miR‐196b‐5p suppresses the differentiation of osteoblasts through targeting SEMA3A/β‐catenin signaling. Additionally, it promotes osteoclast formation through modulating SEMA3A and RANKL/OPG expression in osteoblastic cells.