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

Shi-Kai Feng; Tuan-Hui Chen; Hong-Ming Li; Jia Cao; Dong-Biao Liu; Shan-Shan Rao; Jiang-Hua Liu; Yan Zhang; Zhen-Xing Wang; You-You Li; Yi-Juan Tan; Yi-Wei Liu; Chun-Gu Hong; Zi-Qi Yan; Meng-Lu Chen; Yi-Yi Wang; Hao Yin; Ling Jin; Hui Xie; Zheng-Guang Wang; Yong Zhou

doi:10.1016/j.mce.2021.111373

Deficiency of Omentin-1 leads to delayed fracture healing through excessive inflammation and reduced CD31^hiEmcn^hi vessels

Mol Cell Endocrinol. 2021 Aug 20:534:111373. doi: 10.1016/j.mce.2021.111373. Epub 2021 Jun 23.

Authors

Shi-Kai Feng¹, Tuan-Hui Chen², Hong-Ming Li³, Jia Cao², Dong-Biao Liu⁴, Shan-Shan Rao⁵, Jiang-Hua Liu³, Yan Zhang⁶, Zhen-Xing Wang², You-You Li³, Yi-Juan Tan², Yi-Wei Liu³, Chun-Gu Hong², Zi-Qi Yan⁷, Meng-Lu Chen¹, Yi-Yi Wang³, Hao Yin³, Ling Jin³, Hui Xie⁸, Zheng-Guang Wang⁹, Yong Zhou¹⁰

Affiliations

¹ Department of Sports Medicine, 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.
² Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
³ Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁴ Department of Orthopedics, the Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
⁵ Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Xiangya School of Nursing, Central South University, Changsha, Hunan, 410013, China.
⁶ Department of Sports Medicine, 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, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
⁷ Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁸ Department of Sports Medicine, 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 Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Bone Joint Degeneration and Injury, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. Electronic address: huixie@csu.edu.cn.
⁹ Department of Orthopedics, the Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China. Electronic address: xy3yywzg@csu.edu.cn.
¹⁰ Department of Orthopedics, the Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China. Electronic address: xy3yyzy@csu.edu.cn.

PMID: 34174367
DOI: 10.1016/j.mce.2021.111373

Abstract

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 (PDGF-BB) and osteogenesis-promoting vessels that are strongly positive for CD31 and Endomucin (CD31^hiEmcn^hi) in the fracture area. In vitro, omentin-1 treatment suppressed the ability of the tumor necrosis factor-α (TNF-α)-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 CD31^hiEmcn^hi vessel formation.

Keywords: CD31(hi)Emcn(hi) vessel; Fracture healing; Inflammation; Omentin-1; PDGF-BB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement
Cytokines / genetics*
Disease Models, Animal
Female
Femoral Fractures / etiology
Femoral Fractures / genetics*
Femoral Fractures / immunology
Fracture Healing*
GPI-Linked Proteins / genetics*
Gene Knockout Techniques
Lectins / genetics*
Mice
Osteoclasts / metabolism
Osteogenesis
Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
RAW 264.7 Cells
Sialoglycoproteins / metabolism*
X-Ray Microtomography

Substances

Cytokines
Emcn protein, mouse
GPI-Linked Proteins
Itln1 protein, mouse
Lectins
Pecam1 protein, mouse
Platelet Endothelial Cell Adhesion Molecule-1
Sialoglycoproteins