Loss of chemerin triggers bone remodeling in vivo and in vitro
| Autor: | Qingbo Wei, Shiwei Wan, Long Han, Guichen Huang, Wenbing Shang, Yu Zhang, Wen Min, Penghua Fang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Bone metabolism Osteoporosis Bone resorption Bone remodeling Mice Osteoclast Internal medicine medicine Animals Chemerin Molecular Biology Cells Cultured Cell Proliferation Mice Knockout Bone mineral Osteoblasts biology Chemistry Metabolic dysfunction Cell Differentiation Osteoblast Cell Biology medicine.disease RC31-1245 Mice Inbred C57BL Endocrinology medicine.anatomical_structure RANKL biology.protein Intercellular Signaling Peptides and Proteins Female Original Article Bone Remodeling Chemokines |
| Zdroj: | Molecular Metabolism Molecular Metabolism, Vol 53, Iss, Pp 101322-(2021) |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2021.101322 |
| Popis: | Objective It was reported that chemerin as an adipocyte-secreted protein could regulate bone resorption and bone formation. However, the specific molecular and gene mechanism of the chemerin role is unclear. The aim of this study is to evaluate the role of chemerin in bone metabolism. Methods In the present study, we investigated the effects of chemerin on bone remodeling in rarres2 knockout (Rarres2−/−) mice and examined the role of chemerin as a determinant of osteoblast and osteoclast differentiation in Mc3t3-E1 and Raw264.7 cell lines. Results The results showed that the bone mineral density and volume score, trabecular thickness, weight and bone formation marker BALP increased, but Tb.Sp and bone resorption marker TRACP-5b decreased in Rarres2−/− mice. Furthermore, the mRNA and protein expression of biomarkers of osteoblasts (β-catenin, RANKL and OPG) significantly increased, but those of osteoclasts (CTSK and RANK) decreased in Rarres2−/− mice. In vitro, chemerin markedly suppressed β-catenin and OPG, but increased RANKL, CTSK and RANK expression. Moreover, knockdown of chemerin using RNA interference enhanced osteoblastogenesis genes and inhibited osteoclastogenesis genes in Mc3t3-E1 and Raw264.7 cells. Conclusions Taken together, these data suggest an inhibitive effect of chemerin on osteoblast differentiation and proliferation through inhibition of Wnt/β-catenin signaling, as well as a stimulative effect of chemerin on osteoclast differentiation and proliferation via activation of RANK signaling. The maintenance of a low chemerin level may be a strategy for the prevention and treatment of osteoporosis. Graphical abstract Image 1 Highlights • The bone mineral density and volume score and the trabecular thickness were significantly increased in Rarres2−/− mice. • Chemerin markedly suppressed β-catenin and OPG, and increased RANKL, CTSK as well as RANK expression. • The enhancement of osteoclastogenesis genes by chemerin were blocked by knockdown of chemerin in Raw264.7 cells. • An inhibitive effect of chemerin on osteoblast differentiation through inhibition of Wnt/β-catenin signaling. • The stimulative effect of chemerin on osteoclast differentiation and proliferation via activation of RANK signaling. |
| Databáze: | OpenAIRE |
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