HIF1 alpha Promotes BMP9-Mediated Osteoblastic Differentiation and Vascularization by Interacting with CBFA1

作者全名："Li, Yuwan; Liu, Ziming; Wang, Hong-De; Zhang, Jun; Lin, Miaoyuan; Yang, Jianye; Huang, Jiaxing; Yan, Wenqiang; Ao, Yingfang"

作者地址："[Li, Yuwan; Liu, Ziming; Wang, Hong-De; Yan, Wenqiang; Ao, Yingfang] Peking Univ, Peking Univ Third Hosp, Dept Sports Med, Beijing Key Lab Sports Injuries,Inst Sports Med, Beijing 100191, Peoples R China; [Zhang, Jun; Yang, Jianye; Huang, Jiaxing] Chongqing Med Univ, Dept Orthopaed, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Lin, Miaoyuan] Zunyi Med Univ, Dept Orthopaed, Affiliated Hosp 1, Zunyi 563000, Guizhou, Peoples R China"

通信作者："Ao, YF (通讯作者)，Peking Univ, Peking Univ Third Hosp, Dept Sports Med, Beijing Key Lab Sports Injuries,Inst Sports Med, Beijing 100191, Peoples R China."

来源：BIOMED RESEARCH INTERNATIONAL

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000868606200001

JCR分区：Q3

影响因子：3.246

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Bone morphogenetic protein 9 (BMP9) as the most potent osteogenic molecule which initiates the differentiation of stem cells into the osteoblast lineage and regulates angiogenesis, remains unclear how BMP9-regulated angiogenic signaling is coupled to the osteogenic pathway. Hypoxia-inducible factor 1 alpha (HIF1 alpha) is critical for vascularization and osteogenic differentiation and the CBFA1, known as runt-related transcription factor 2 (Runx2) which plays a regulatory role in osteogenesis. This study investigated the combined effect of HIF1 alpha and Runx2 on BMP9-induced osteogenic and angiogenic differentiation of the immortalized mouse embryonic fibroblasts (iMEFs). The effect of HIF1 alpha and Runx2 on the osteogenic and angiogenic differentiation of iMEFs was evaluated. The relationship between HIF1 alpha- and Runx2-mediated angiogenesis during BMP9-regulated osteogenic differentiation of iMEFs was evaluated by ChIP assays. We demonstrated that exogenous expression of HIF1 alpha and Runx2 is coupled to potentiate BMP9-induced osteogenic and angiogenic differentiation both in vitro and animal model. Chromatin immunoprecipitation assays (ChIP) showed that Runx2 is a downstream target of HIF1 alpha that regulates BMP9-mediated osteogenesis and angiogenic differentiation. Our findings reveal that HIF1 alpha immediately regulates Runx2 and may originate an essential regulatory thread to harmonize osteogenic and angiogenic differentiation in iMEFs, and this coupling between HIF1 alpha and Runx2 is essential for bone healing."

基金机构：China Postdoctoral Science Foundation; [2020M680258]

基金资助正文：AcknowledgmentsThis work was supported by the China Postdoctoral Science Foundation (No. 2020M680258).