title: Polymethylmethacrylate particle exposure causes changes in p38 MAPK and TGF-beta signaling in differentiating MC3T3-E1 cells.
abstract: Periprosthetic osteolysis of joint replacements caused by wear debris is a significant complication of joint replacements. Polymethylmethacrylate (PMMA) particles have been shown to inhibit osteogenic differentiation, but the molecular mechanism has not been previously determined. In this study, we exposed differentiating MC3T3-E1 preostoblast cells to PMMA particles and determined the changes that occurred with respect to p38 mitogen-activated protein kinase (MAPK) activity and the transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP) signaling pathways. In the absence of particles, MC3T3-E1 cells demonstrate activation of p38 MAPK on day 8 of differentiation; however, when treated with PMMA particles, differentiating MC3T3-E1 cells demonstrate the suppression of p38 activity on day 8 and show activation of p38 on days 1 and 4. On day 4 of particle exposure, the differentiating MC3T3-E1 cells show significant downregulation of TGF-beta1 expression, which is involved in osteoblast differentiation, and a significant upregulation of the expression of BMP3 and Sclerostin (SOST), which are negative regulators of osteoblast differentiation. By day 8 of particle exposure, the changes in TGF-beta1, BMP3, and SOST expression are opposite of those seen on day 4. This study has demonstrated the distinct changes in the molecular profile of MC3T3-E1 cells during particle-induced inhibition of osteoblast differentiation. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University Medical Center, Stanford, California, USA. goodbone@stanford.edu
authors.forename: Gene K
authors.initials: GK
authors.lastname: Ma
authors.forename: Richard
authors.initials: R
authors.lastname: Chiu
authors.forename: Zhinong
authors.initials: Z
authors.lastname: Huang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Pearl
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.forename: R Lane
authors.initials: RL
authors.lastname: Smith
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001843:Bone Cements / Q000494:pharmacology*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D008422:Materials Testing; D051379:Mice; D010316:Particle Size; D019904:Polymethyl Methacrylate / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D001843:Bone Cements; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D019904:Polymethyl Methacrylate; D048051:p38 Mitogen-Activated Protein Kinases