Li Ang,Bao Quanwei,Chen Sixu,Liu Huayu,Li Junfeng,Chen Hui,Zhong Xiaozheng,Zong Zhaowen.Bone morphogenetic protein receptor 1A-mediated signaling pathway regulates osteoblast terminal differentiation in vivo[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(15):1717-1721.
Li Ang,Bao Quanwei,Chen Sixu,Liu Huayu,Li Junfeng,Chen Hui,Zhong Xiaozheng,Zong Zhaowen.Bone morphogenetic protein receptor 1A-mediated signaling pathway regulates osteoblast terminal differentiation in vivo[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(15):1717-1721.DOI:
Objective To investigate the role of bone morphogenetic protein receptor 1A(BMPR1A)-mediated signaling in osteoblast terminal differentiation in vivo. Methods LoxP/Cre system was used to conditionally knock out BMPR1A in osteoblast by cross-breeding Cre mice (3.2 kb collagen Ⅰ as promoter) with BMPR1A LoxP+/+ mice.Their offsprings lacking active Cre was grouped into control. Von Kossa staining
Alizarin red staining and scanning electron microscopy were carried out to observe the mineralization of osteoblast. Masson staining and sirius red staining were used for evaluation of collagen synthesis ability in osteoblast. Immunohistochemistry staining and cell cycle analysis were employed to mechanistically study terminal differentiation of osteoblast. Results Compared with control group
we found that BMPR1A knockout mice had attenuated bone mineralization associated with decreased intercellular connection and enlarged intercellular gap. Masson staining showed reduced collagen synthesis with irregular collagenic arrangement. In addition
fibroblast growth factor 23 (FGF23) and osteopontin (OPN) were upregulated. Cell cycle analysis found that a large number of osteoblast arrested at G phrase of cell cycle
which partly impeded the terminal differentiation of osteoblast. Conclusion BMPR1A plays an important role in osteoblast terminal differentiation.Knocking out BMPR1A leads to decreased bone mineralization and collagen synthesis.