Osteocytic HIF-1α Pathway Manipulates Bone Micro-structure and Remodeling via Regulating Osteocyte Terminal Differentiation
Kaizhe Chen, Jian Zhao, Minglong Qiu, Lianfang Zhang, Kai Yang, Leilei Chang, Peng Jia, Qi Jin, 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.