Abstract
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 CD31hiendomucinhi (CD31hiEMCNhi) endothelium has been identified to promote bone formation, together with osteoblast development. However, the role of microRNA143 in the generation of CD31hi EMCNhi endothelium and bone formation remains unknown. In this study, we found that miR-143 was expressed both in osteoblast cells and CD31hiEMCNhi endothelial cells. Serum miR-143 level was negatively correlated with age in humans. Overexpression of miR-143 promoted osteoblast formation and angiogenic effects. Furthermore, CD31hiEmcnhi 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.
Highlights
Bone formation is directly regulated by the number and function of osteoblasts and osteoclasts[1,2,3]
Bglap and Alp expression levels were decreased by miR-143 deficiency and rescued by knockdown of HDAC7 in vivo (Supplementary Fig. S5A, B), which confirming the roles of miR-143 and HDAC7 in osteogenesis. These results demonstrated that miR-143 promoted angiogenesis coupling with osteoblast differentiation by targeting HDAC7
In this study, we found that miR-143 was significantly increased in osteoblast cells and CD31hiEMCNhi endothelial cells and was positively correlated with the bone formation marker genes BGLAP and Alp
Summary
Bone formation is directly regulated by the number and function of osteoblasts and osteoclasts[1,2,3]. Runx[2] is the vital determinant of osteoblast differentiation and its inactivation delays osteoblast differentiation, whereas the low-density lipoprotein receptor-related protein 5 signaling pathway type vessels (CD31hiEMCNhi)—was identified to provide specific molecular signals that promoted bone formation[8]. CD31hiEMCNhi endothelium formed an appropriate niche for both osteoblast and osteoclast development. These H-type vessels can secrete Noggin to mediate osteoprogenitors differentiation[9]. The other signaling pathways that alter the number of CD31hiEMCNhi endothelium are still not fully demonstrated
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