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

作者全名："Xu, Jie; Wu, Xiangmei; Zhu, Huifang; Zhu, Yinghua; Du, Kailong; Deng, Xiaoyan; Wang, Changdong"

作者地址："[Xu, Jie; Zhu, Huifang; Du, Kailong; Deng, Xiaoyan; Wang, Changdong] Chongqing Med Univ, Coll Basic Med, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [Wu, Xiangmei] Chongqing Med Univ, Coll Basic Med, Mol Med & Canc Res Ctr, Dept Physiol, Chongqing 400016, Peoples R China; [Zhu, Yinghua] Chongqing Univ, Cent Hosp, Chongqing Emergency Med Ctr, Dept Prehosp Emergency, Chongqing 400014, Peoples R China"

通信作者："Wang, CD (通讯作者)，Chongqing Med Univ, Coll Basic Med, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China."

来源：MEDICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001159693500001

JCR分区：Q2

影响因子：2.8

年份：2024

卷号：41

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：C-reactive protein; Inflammation; Hedgehog; Primary cilia; Osteoblastic differentiation

摘要："Inflammation disrupts bone metabolism and leads to bone damage. C-reactive protein (CRP) is a typical inflammation marker. Although CRP measurement has been conducted for many decades, how osteoblastic differentiation influences molecular mechanisms remains largely unknown. The present study attempted to investigate the effects of CRP on primary cultured osteoblast precursor cells (OPCs) while elucidating the underlying molecular mechanisms. OPCs were isolated from suckling Sprague-Dawleyrats. Fewer OPCs were observed after recombinant C-reactive protein treatment. In a series of experiments, CRP inhibited OPC proliferation, osteoblastic differentiation, and the OPC gene expression of the hedgehog (Hh) signaling pathway. The inhibitory effect of CRP on OPC proliferation occurred via blockade of the G1-S transition of the cell cycle. In addition, the regulation effect of proto cilium on osteoblastic differentiation was analyzed using the bioinformatics p. This revealed the primary cilia activation of recombinant CRP effect on OPCs through in vitro experiments. A specific Sonic Hedgehog signaling agonist (SAG) rescued osteoblastic differentiation inhibited by recombinant CRP. Moreover, chloral hydrate, which removes primary cilia, inhibited the Suppressor of Fused (SUFU) formation and blocked Gli2 degradation. This counteracted osteogenesis inhibition caused by CRP. Therefore, these data depict that CRP can inhibit the proliferation and osteoblastic differentiation of OPCs. The underlying mechanism could be associated with primary cilia activation and Hh pathway repression."

基金机构：Chongqing Natural Science Foundation of China

基金资助正文：No Statement Available