Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y.

Abstract

A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age- and menopause-associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging- and ovariectomy (OVX)-induced bone-fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS-induced regulation of BMSC fate and bone-fat balance. γ-Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging- and OVX-induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS-induced regulation of osteocyte NPY.

• Authors: Yan Zhang, Chun-Yuan Chen, Yi-Wei Liu, Shan-Shan Rao, Yi-Juan Tan, Yu-Xuan Qian, Kun Xia, Jie Huang, Xi-Xi Liu, Chun-Gu Hong, Hao Yin, Jia Cao, Shi-Kai Feng, Ze-Hui He, You-You Li, Zhong-Wei Luo, Ben Wu, Zi-Qi Yan, Tuan-Hui Chen, Meng-Lu Chen, Yi-Yi Wang, Zhen-Xing Wang, Zheng-Zhao Liu, Ming-Jie Luo, Xiong-Ke Hu, Ling Jin, Teng-Fei Wan, Tao Yue, Si-Yuan Tang, Hui Xie
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 8 Issue 24 Pg. e2100808 (12 2021) ISSN: 2198-3844 [Electronic] Germany
• PMID: 34719888 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• Neuropeptide Y

Topics

• Adipocytes (metabolism)
• Adipogenesis (physiology)
• Animals
• Bone and Bones (metabolism, physiopathology)
• Disease Models, Animal
• Female
• Male
• Mice
• Mice, Inbred C57BL
• Neuropeptide Y (metabolism)
• Osteoblasts (metabolism)
• Osteocytes (metabolism)
• Osteogenesis (physiology)
• Osteoporosis (metabolism, physiopathology)