Vol. 43, No. 2, October 1997 BIOCHEMISTRY and MOLECULAR BIOLOGY INTERNATIONAL Pages339-346 THE INCREASED LEVEL OF PDGF-A CONTRIBUTES TO THE INCREASED PROLIFERATION INDUCED BY MECHANICAL STIMULATION IN OSTEOBLASTIC CELLS # Reprint request to: *Current Address: Wei Wang, Hongming Zhuang*, Craig L. Levitz, Huijun Fan, Richard M. Seldes, A. David Tahernia, Carl T. Brighton# Department of Orthopaedic Surgery University of Pennsylvania School of Medicine 424 Edward J. Stemmler Hall 36th and Hamilton Walk Philadelphia, PA 19104-6081 Carl T. Brighton, M.D., Ph.D. phone: (215) 898-8653; fax: (215) 573-2133 Department of Pathology and Laboratory Medicine Allegheny University of Health Sciences, Philadelphia, PA 19129 Received July 2, 1997 Summary: Mechanical stimulation can prompt healing of bone fractures. However, it is largely unknown how osteogenesis is promoted by mechanical stimulation. In this study, we found that mechanical strain-inducedl proliferation of osteoblastic cells (MC3T3-E1) accompanied increased levels of platelet-derived growth factor-A (PDGF-A) mRNA, determined by quantitative reverse transcription/polymerase chain reaction. In addition, neomycin and W-7, which blocked mechanical strain-induced proliferation of the osteoblast cells, also blocked mechanical stimulation-induced elevation of PDGF-A mRNA. Finally, an antibody against PDGF can inhibit physical stimulation-induced proliferation of MC3T3-E1 cells, suggesting that the increased MC3T3-E1 cells produced by mechanical stimulation at least partially depends on the increased activity of PDGF. Key Words: PDGF-A, osteoblast, mechanical strain INTRODUCTION Bone is exquisitely responsive to its mechanical environment. Mechanical stimulation can increase bone growth(I-5). In the past decade, great efforts have been made to understand how mechanical stimulus leads to increased proliferation of bone cells(6-16). However, the mechanism of action at the cellular and molecular level in osteogenesis that is induced by mechanical stimulation is still unclear. PDGF-A has numerous and diverse effects on osteoblastic cells(17-21). Especially, PDGF has shown to elicit the proliferation of bone cells(22, 23). Considering that both PDGF and mechanical signals are able to prompt bone growth, we wished to evaluate the possible role of PDGF-A in the proliferative response of osteoblasts to mechanical strain in this study. 339 1039 9712/97/020339~8505.00/0 Copyright 9 1997 by Academic Press Australia. All rights ~[ reproduction in any fmwl reserved.