Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y

  • Adv Sci (Weinh). 2021 Dec;8(24):e2100808. doi: 10.1002/advs.202100808.
Yan Zhang  1  2  3  4 ,  Chun-Yuan Chen  1  2 ,  Yi-Wei Liu  1  2  4 ,  Shan-Shan Rao  2  5 ,  Yi-Juan Tan  2 ,  Yu-Xuan Qian  1  2 ,  Kun Xia  1  2 ,  Jie Huang  1  2 ,  Xi-Xi Liu  6 ,  Chun-Gu Hong  2 ,  Hao Yin  1  2 ,  Jia Cao  1  2 ,  Shi-Kai Feng  1  2  4 ,  Ze-Hui He  1  2 ,  You-You Li  1  2 ,  Zhong-Wei Luo  1  2 ,  Ben Wu  1 ,  Zi-Qi Yan  1 ,  Tuan-Hui Chen  1 ,  Meng-Lu Chen  4 ,  Yi-Yi Wang  1  2 ,  Zhen-Xing Wang  1  2 ,  Zheng-Zhao Liu  1  2  4  7 ,  Ming-Jie Luo  2  5 ,  Xiong-Ke Hu  1  2 ,  Ling Jin  1  2 ,  Teng-Fei Wan  1  2 ,  Tao Yue  1  2 ,  Si-Yuan Tang  5 ,  Hui Xie  1  2  4  7  8  9
Affiliations
  • 1. Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • 2. Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • 3. Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 4. Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • 5. Xiangya School of Nursing, Central South University, Changsha, Hunan, 410013, China.
  • 6. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
  • 7. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • 8. Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Xiangya Hospital, Central South University, Changsha, Changsha, Hunan, 410008, China.
  • 9. Hunan Key Laboratory of Bone Joint Degeneration and Injury, Xiangya Hospital, Central South University, Changsha, Changsha, Hunan, 410008, China.
PMID: 34719888 DOI: 10.1002/advs.202100808
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.

Keywords
adipogenesis; autonomic nervous system; bone marrow mesenchymal stem/stromal cells; neuropeptide Y; osteocyte; osteogenesis.
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