Osteocytic HIF-1α Pathway Manipulates Bone Micro-structure and Remodeling via Regulating Osteocyte Terminal Differentiation

骨细胞 HIF-1α 通路通过调节骨细胞终末分化来操纵骨微结构和重塑

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作者:Kaizhe Chen, Jian Zhao, Minglong Qiu, Lianfang Zhang, Kai Yang, Leilei Chang, Peng Jia, Jin Qi, Lianfu Deng, Changwei Li

Abstract

The activation of hypoxia-inducible factor 1α (HIF-1α) signaling has promising implications for the treatment of bone diseases such as osteoporosis and skeletal fractures. However, the effects of manipulating HIF-1α pathway on bone micro-structure and remodeling should be fully studied before the clinical application of therapeutics that interfere with the HIF-1α pathway. In this study, we found that osteocyte-specific HIF-1α pathway had critical role in manipulating bone mass accrual, bone material properties and micro-structures, including bone mineralization, bone collagen fiber formation, osteocyte/canalicular network, and bone remodeling. In addition, our results suggest that osteocyte-specific HIF-1α pathway regulates bone micro-structure and remodeling via impairing osteocyte differentiation and maturation.

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