Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis

Author:

Qian Yu‐Xuan12,Rao Shan‐Shan12,Tan Yi‐Juan12,Wang Zun12,Yin Hao12,Wan Teng‐Fei12,He Ze‐Hui12,Wang Xin12,Hong Chun‐Gu12,Zeng Hai‐Jin12,Luo Yi12,Duan Yan‐Xin12,Zhu Hao12,Hu Xin‐Yue3,Zou Ling12,Zhang Yan14,Liu Bing‐Bing5,Wang Zhen‐Xing12,Du Wei126,Chen Chun‐Yuan127,Xie Hui127ORCID

Affiliation:

1. Department of Orthopedics Movement System Injury and Repair Research Center Xiangya Hospital Central South University Changsha Hunan 410008 China

2. Hunan Key Laboratory of Angmedicine Changsha Hunan 410008 China

3. Department of Respiratory Medicine Xiangya Hospital Central South University Changsha Hunan 410008 China

4. Department of Pediatrics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

5. School of Computer Science and Engineering Central South University Changsha Hunan 410083 China

6. Department of Rehabilitation Xiangya Hospital Central South University Changsha Hunan 410008 China

7. National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha Hunan 410008 China

Abstract

AbstractOsteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)‐ or natural aging‐induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY‐abundant culture medium of osteocytes (OCY‐CM) from osteoarthritic mice possess pro‐inflammatory, pro‐osteoclastic, and pro‐neurite outgrowth effects, while OCY‐CM from the intermittent fasting‐treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM‐induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

Funder

National Natural Science Foundation of China

Hunan Provincial Innovation Foundation for Postgraduate

Publisher

Wiley

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