Deficiency of Omentin-1 leads to delayed fracture healing through excessive inflammation and reduced CD31hiEmcnhi vessels

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:534

Article

Feng, Shi-Kai^1,2  Chen, Tuan-Hui²  Li, Hong-Ming^2,3  Cao, Jia²  Liu, Dong-Biao⁴  Rao, Shan-Shan^2,5  Liu, Jiang-Hua^2,3  Zhang, Yan^1,2,7  Wang, Zhen-Xing²  Li, You-You^2,3  Tan, Yi-Juan²  Liu, Yi-Wei^2,3  Hong, Chun-Gu²  Yan, Zi-Qi^2,6  Chen, Meng-Lu^1,2  Wang, Yi-Yi^2,3  Yin, Hao^2,3  Jin, Ling^2,3  Xie, Hui^1,2,3,8,9,10  Wang, Zheng-Guang⁴  Zhou, Yong⁴ 

[1] Cent South Univ, Xiangya Hosp, Dept Sports Med, Changsha 410008, Hunan, Peoples R China

[2] Cent South Univ, Xiangya Hosp, Movement Syst Injury & Repair Res Ctr, Changsha 410008, Hunan, Peoples R China

[3] Cent South Univ, Xiangya Hosp, Dept Orthoped, Changsha 410008, Hunan, Peoples R China

[4] Cent South Univ, Xiangya Hosp 3, Dept Orthoped, Changsha 410013, Hunan, Peoples R China

[5] Cent South Univ, Xiangya Sch Nursing, Changsha 410013, Hunan, Peoples R China

[6] Cent South Univ, Xiangya Hosp, Dept Stomatol, Changsha 410008, Hunan, Peoples R China

[7] Huazhong Univ Sci & Technol, Union Hosp, Dept Pediat, Wuhan 430022, Hubei, Peoples R China

[8] Hunan Key Lab Organ Injury Aging & Regenerat Med, Changsha 410008, Hunan, Peoples R China

[9] Hunan Key Lab Bone Joint Degenerat & Injury, Changsha 410008, Hunan, Peoples R China

[10] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China

关键词: Fracture healing;    Inflammation;    Omentin-1;    PDGF-BB;    CD31(hi)Emcn(hi) vessels;   

DOI  :  10.1016/j.mce.2021.111373

来源: Elsevier

【 摘 要 】

Fracture healing is a complicated process affected by many factors, such as inflammatory responses and angiogenesis. Omentin-1 is an adipokine with anti-inflammatory properties, but whether omentin-1 affects the fracture healing process is still unknown. Here, by using global omentin-1 knockout (omentin-1-/- ) mice, we demonstrated that omentin-1 deficiency resulted in delayed fracture healing in mice, accompanied by increased inflammation and osteoclast formation, and decreased production of platelet-derived growth factor-BB (PDGFBB) and osteogenesis-promoting vessels that are strongly positive for CD31 and Endomucin (CD31hiEmcnhi) in the fracture area. In vitro, omentin-1 treatment suppressed the ability of the tumor necrosis factor-alpha (TNF alpha)-activated macrophages to stimulate multi-nuclear osteoclast formation, resulting in a significant increase in the generation of mono-nuclear preosteoclasts and PDGF-BB, a pro-angiogenic protein that is abundantly secreted by preosteoclasts. PDGF-BB significantly augmented endothelial cell proliferation, tube formation and migration, whereas direct treatment with omentin-1 did not induce obvious effects on angiogenesis activities of endothelial cells. Our study suggests a positive role of omentin-1 in fracture healing, which may be associated with the inhibition of inflammation and stimulation of preosteoclast PDGF-BB-mediated promotion of CD31hiEmcnhi vessel formation.

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