Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y,Advanced Science

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Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y
Advanced Science ( IF 14.3 ) Pub Date : 2021-10-31 , 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}

Affiliation

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Xiangya School of Nursing, Central South University, Changsha, Hunan, 410013, China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Xiangya Hospital, Central South University, Changsha, Changsha, Hunan, 410008, China.
Hunan Key Laboratory of Bone Joint Degeneration and Injury, Xiangya Hospital, Central South University, Changsha, Changsha, Hunan, 410008, China.

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.

中文翻译：

骨细胞神经肽 Y 对骨脂肪失衡的神经元诱导

骨髓间充质干/基质细胞 (BMSCs) 从成骨细胞到脂肪细胞的分化转换有助于与年龄和更年期相关的骨质流失和骨髓肥胖。在这里，我们发现骨细胞是最丰富的骨细胞，通过分泌神经肽 Y (NPY) 促进脂肪生成并抑制 BMSCs 的成骨，其表达随着衰老和骨质疏松症而增加。骨细胞中 NPY 的缺失会产生高骨量表型，并减轻衰老和卵巢切除术 (OVX) 诱导的小鼠骨脂肪失衡。骨细胞 NPY 的产生受自主神经系统 (ANS) 的控制，并且骨细胞 NPY 缺失阻断了 ANS 诱导的 BMSC 命运和骨脂肪平衡的调节。γ-谷维素，一种临床使用的 ANS 调节剂，在对照小鼠中显着增加骨形成并逆转衰老和 OVX 诱导的骨细胞 NPY 过度产生和骨髓肥胖，但在缺乏骨细胞 NPY 的小鼠中没有。该研究提出了一种通过 ANS 诱导的骨细胞 NPY 调节的神经元控制骨代谢的新模式。

更新日期：2021-12-22

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