Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai, China.
Guangdong Key Lab of Orthopedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Hospital of Orthopedics, General Hospital of Southern Theater Command of PLA, 111 Liuhua Road, Guangzhou, Guangdong, 510010, China.
Cell Death Dis. 2020 Mar 9;11(3):179. doi: 10.1038/s41419-020-2377-4.
The regulation of bone formation and detailed mechanisms are still largely elusive, and the roles of microRNAs in this process have attracted much attention. Recently, a specific subtype of CD31endomucin (CD31EMCN) endothelium has been identified to promote bone formation, together with osteoblast development. However, the role of microRNA143 in the generation of CD31 EMCN endothelium and bone formation remains unknown. In this study, we found that miR-143 was expressed both in osteoblast cells and CD31EMCN endothelial cells. Serum miR-143 level was negatively correlated with age in humans. Overexpression of miR-143 promoted osteoblast formation and angiogenic effects. Furthermore, CD31Emcn vessels and osteoblast formation were significantly inhibited in miR-143 knockout mice. Mechanistically, inhibitor HDAC7 was directly targeted by miR-143 and knockdown of HDAC7 was found to rescue the function of miR-143 deficiency. Thus, miR-143 promotes angiogenesis coupling with osteoblast differentiation by targeting HDAC7, which may serve as a potential target in angiogenic and osteogenic diseases.
骨形成的调节及其详细机制在很大程度上仍难以捉摸,microRNAs 在这一过程中的作用引起了广泛关注。最近,已经确定了一种特定的 CD31endomucin(CD31EMCN)内皮细胞亚型,其共同促进骨形成和成骨细胞的发育。然而,microRNA143 在 CD31 EMCN 内皮细胞生成和骨形成中的作用仍不清楚。在这项研究中,我们发现 miR-143 在成骨细胞和 CD31EMCN 内皮细胞中均有表达。血清 miR-143 水平与人类年龄呈负相关。miR-143 的过表达促进成骨细胞的形成和血管生成作用。此外,miR-143 敲除小鼠的 CD31Emcn 血管和成骨细胞形成明显受到抑制。在机制上,miR-143 直接靶向 HDAC7,并且发现敲低 HDAC7 可以挽救 miR-143 缺失的功能。因此,miR-143 通过靶向 HDAC7 促进血管生成与成骨细胞分化,这可能成为血管生成和成骨疾病的潜在治疗靶点。