title: Effects of C-reactive protein on bone cells.
abstract: OBJECTIVE
  Inflammatory processes are involved in bone remodeling. C-reactive protein (CRP) is an acute phase reactant that reflects different degrees of inflammation. Accumulating evidence suggests that CRP is an inflammatory marker and a direct cause of disease. Therefore, we examined the direct effects of CRP on bone cells.
  
  
  METHODS
  We used RAW 264.7 cells to evaluate the direct effects of CRP on osteoclast differentiation. We carried out alkaline phosphatase (ALP) and bone nodule formation assays using MC3T3-E1 cells to evaluate osteoblast differentiation. Expression of osteoclast-specific and osteoblast-specific genes and effects on cell signaling pathways associated with cell differentiation were analyzed by reverse transcription polymerase chain reaction and Western blotting.
  
  
  RESULTS
  CRP significantly and dose-dependently inhibited TRAP-positive multinucleated cell formation in RANKL-induced RAW 264.7 cell cultures. We observed suppression of p38, ERK and AKT mitogen-activated protein kinases induced by RANKL in Western blots after CRP treatment of RAW 264.7 cells. CRP also suppressed ALP activity and mineralization by Alizarin red S staining of MC3T3-E1 cell cultures. CRP suppressed osteoclast-specific and osteoblast-specific genes. Furthermore, CRP increased interferon beta (IFN-β) mRNA expression and protein levels in RAW 264.7 and MC3T3-E1 cells, and these effects were suppressed by oxPAPC, an inhibitor of Toll-like receptor (TLR) signaling.
  
  
  CONCLUSIONS
  These data indicated that CRP may have a direct role on osteoclast and osteoblast differentiation via TLR signaling pathways.
authors.affiliation: Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Cho
authors.affiliation: Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kyoung Hee
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chi Hyuk
authors.initials: CH
authors.lastname: Oh
authors.affiliation: Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors.forename: You Cheol
authors.initials: YC
authors.lastname: Hwang
authors.affiliation: Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors.forename: In-Kyung
authors.initials: IK
authors.lastname: Jeong
authors.affiliation: Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kyu Jeung
authors.initials: KJ
authors.lastname: Ahn
authors.affiliation: Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Republic of Korea. Electronic address: chunghoyeon@khu.ac.kr.
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000276:immunology*; D002454:Cell Differentiation; D002460:Cell Line; D007249:Inflammation / Q000276:immunology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000276:immunology*; D010010:Osteoclasts / Q000166:cytology / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D051193:Toll-Like Receptors; D002097:C-Reactive Protein
keywords: C-reactive protein; Osteoblast; Osteoclast; Toll-like receptor