Loss of chemerin triggers bone remodeling in vivo and in vitro

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.

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.

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.

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.