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Omentin-1 prevents inflammation-induced osteoporosis by downregulating the pro-inflammatory cytokines

Bone Research 2018年第2期6卷 177-188页

作者： Shan-Shan Rao Yin Hu Ping-Li Xie Jia Cao Zhen-Xing Wang Jiang-Hua Liu Hao Yin Jie Huang Yi-Juan Tan Juan Luo Ming-Jie Luo Si-Yuan Tang Tuan-Hui Chen Ling-Qing Yuan Er-Yuan Liao Ran Xu Zheng-Zhao Liu Chun-Yuan Chen Hui Xie Movement System Injury and Repair Research Center Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Spine Surgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Forensic Science School of Basic Medical SciencesCentral South UniversityChangshaHunan 410013China Xiangya Nursing School Central South UniversityChangshaHunan 410013China Second Xiangya Hospital Central South UniversityChangshaHunan 410011China Hunan Key Laboratory of Organ Injury Aging and Regenerative MedicineChangshahunan 410008China Department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China China Orthopedic Regenerative Medicine Group(CORMed) ChangshaHunanChina

Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.

关键词： TNF Omentin-1 prevents inflammation-induced osteoporosis downregulating pro-inflammatory cytokines RANKL

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