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Polymethylmethacrylate particle exposure causes changes in p38 MAPK and TGF‐β signaling in differentiating MC3T3‐E1 cells
Author(s) -
Ma Gene K.,
Chiu Richard,
Huang Zhig,
Pearl Jeremy,
Ma Ting,
Smith R. Lane,
Goodman Stuart B.
Publication year - 2010
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32686
Subject(s) - osteoblast , downregulation and upregulation , p38 mitogen activated protein kinases , microbiology and biotechnology , materials science , sclerostin , transforming growth factor , osteolysis , mapk/erk pathway , signal transduction , biology , medicine , biochemistry , in vitro , gene , dentistry , wnt signaling pathway
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)‐β1 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‐β1 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‐β1, 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. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010