PMID- 38345752
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240227
IS  - 1559-131X (Electronic)
IS  - 1357-0560 (Linking)
VI  - 41
IP  - 3
DP  - 2024 Feb 12
TI  - CRP inhibits the osteoblastic differentiation of OPCs via the up-regulation of 
      primary cilia and repression of the Hedgehog signaling pathway.
PG  - 72
LID - 10.1007/s12032-024-02301-z [doi]
AB  - 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.
CI  - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Xu, Jie
AU  - Xu J
AD  - Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer 
      Research Center, College of Basic Medicine, Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Wu, Xiangmei
AU  - Wu X
AD  - Department of Physiology, Molecular Medicine and Cancer Research Center, College 
      of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.
FAU - Zhu, Huifang
AU  - Zhu H
AD  - Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer 
      Research Center, College of Basic Medicine, Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Zhu, Yinghua
AU  - Zhu Y
AD  - Department of Pre-Hospital Emergency, Chongqing Emergency Medical Center, Central 
      Hospital of Chongqing University, Chongqing, 400014, China.
FAU - Du, Kailong
AU  - Du K
AD  - Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer 
      Research Center, College of Basic Medicine, Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Deng, Xiaoyan
AU  - Deng X
AD  - Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer 
      Research Center, College of Basic Medicine, Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Wang, Changdong
AU  - Wang C
AUID- ORCID: 0000-0002-2595-1369
AD  - Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer 
      Research Center, College of Basic Medicine, Chongqing Medical University, 
      Chongqing, 400016, China. wangchangdong@cqmu.edu.cn.
LA  - eng
GR  - CSTB2022NSCQ-MSX0945/Chongqing Natural Science Foundation of China/
GR  - cstc2014jcyjA10024/Chongqing Postdoctoral Science Foundation/
GR  - 20200112/the first scientific research plan of Yuzhong District, Chongqing in 
      2020/
GR  - CYS19204/Jiangsu Agricultural Science and Technology Independent Innovation Fund/
GR  - 20125503120015/Specialized Research Fund for the Doctoral Program of Higher 
      Education of China/
GR  - CY170402/Key Laboratory of Industrial Internet of Things and Networked Control, 
      Ministry of Education/
GR  - 2022-2/the scientific research project of Chunhui plan in ministry of education 
      the people's republic of china/
PT  - Journal Article
DEP - 20240212
PL  - United States
TA  - Med Oncol
JT  - Medical oncology (Northwood, London, England)
JID - 9435512
RN  - 0 (Hedgehog Proteins)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Humans
MH  - *Hedgehog Proteins/metabolism
MH  - *C-Reactive Protein/pharmacology/metabolism
MH  - Cilia/metabolism
MH  - Up-Regulation
MH  - Cell Differentiation/physiology
MH  - Signal Transduction
MH  - Osteoblasts/metabolism
MH  - Inflammation/metabolism
OTO - NOTNLM
OT  - C-reactive protein
OT  - Hedgehog
OT  - Inflammation
OT  - Osteoblastic differentiation
OT  - Primary cilia
EDAT- 2024/02/12 15:44
MHDA- 2024/02/12 15:45
CRDT- 2024/02/12 11:14
PHST- 2023/07/03 00:00 [received]
PHST- 2024/01/05 00:00 [accepted]
PHST- 2024/02/12 15:45 [medline]
PHST- 2024/02/12 15:44 [pubmed]
PHST- 2024/02/12 11:14 [entrez]
AID - 10.1007/s12032-024-02301-z [pii]
AID - 10.1007/s12032-024-02301-z [doi]
PST - epublish
SO  - Med Oncol. 2024 Feb 12;41(3):72. doi: 10.1007/s12032-024-02301-z.