CRP inhibits the osteoblastic differentiation of OPCs via the up-regulation of primary cilia and repression of the Hedgehog signaling pathway

Abstract

Abstract Inflammation disrupts bone metabolism and causes bone damage. C-reactive protein (CRP) is a typical marker of inflammation. Although the measurement of CRP has been conducted for many decades, the precise influence on the molecular mechanisms of osteoblastic differentiation remains largely unknown. The present study aimed to investigate the effects of CRP on primary cultured osteoblast precursor cells (OPCs) and elucidate the underlying molecular mechanisms. OPCs were isolated from suckling Sprague-Dawleyrats. Fewer OPCs were observed after treatment with recombinant C-reactive protein. In a series of experiments, it was found that CRP inhibited the proliferation of OPCs, osteoblastic differentiation, and the gene expression of the hedgehog(Hh) signaling pathway in OPCs cells. The inhibitory effect of CRP on the proliferation of OPCs occurred via blockade of the G1-S transition of the cell cycle. In addition, the regulation effect of regulation of protocilium on osteoblasticdifferentiation was analyzed from the perspective of bioinformatics, from which the effect of primary cilia activation of recombinantCRP on OPCs was revealed in in vitro experiments. A specific Sonic Hedgehog signaling agonist (SAG) rescued osteoblasticdifferentiation that was inhibited by recombinantCRP. Moreover, chloral hydrate, which removes primary cilia, inhibited the formation of Suppressor of Fused (SUFU) and blocked the degradation of Gli2, counteracting the inhibition of osteogenesis caused by CRP. Thus, these data indicate that CRP can inhibit the proliferation and osteoblastic differentiation of OPCs. The underlying mechanism may be related to the activation of primary cilia and repression of the Hh pathway.