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

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Abstract

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.

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Upon request, data to support the results of this study can be obtained from the corresponding author.

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Funding

This work was supported by the scientific research project of Chunhui plan in ministry of education the people’s republic of china (2022-2 to Changdong Wang); Chongqing Natural Science Foundation of China (Grant CSTB2022NSCQ-MSX0945; cstc2014jcyjA10024 to Changdong Wang); the first scientific research plan of Yuzhong District, Chongqing in 2020 (Grant: 20200112 to Changdong Wang); the Chongqing Graduate Science and Technology Innovation Project in 2019 (Grant: CYS19204 to Jie Xu); Chinese Higher Education Doctorate Program (Grant: 20125503120015) and Chongqing Education Commission (Grant: CY170402). The content is solely the responsibility of the author and does not necessarily represent the official views of a government with financial support.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China

    Jie Xu, Huifang Zhu, Kailong Du, Xiaoyan Deng & Changdong Wang

  2. Department of Physiology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China

    Xiangmei Wu

  3. Department of Pre-Hospital Emergency, Chongqing Emergency Medical Center, Central Hospital of Chongqing University, Chongqing, 400014, China

    Yinghua Zhu

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  1. Jie Xu
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CW: Conceptualization, Supervision, Funding acquisition, Methodology. JX: Conceptualization, Investigation, Writing—Original Draft, Funding acquisition. HZ: Supervision. XD: Supervision. XW: Supervision. YZ: Software, Resources. KD: Software.

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Correspondence to Changdong Wang.

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Xu, J., Wu, X., Zhu, H. et al. CRP inhibits the osteoblastic differentiation of OPCs via the up-regulation of primary cilia and repression of the Hedgehog signaling pathway. Med Oncol 41, 72 (2024). https://doi.org/10.1007/s12032-024-02301-z

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