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Int J Med Sci 2015; 12(11):905-913. doi:10.7150/ijms.13263

Research Paper

Tension Force Downregulates Matrix Metalloproteinase Expression and Upregulates the Expression of Their Inhibitors through MAPK Signaling Pathways in MC3T3-E1 cells

Yoko Karasawa1, Hideki Tanaka2,3, Kumiko Nakai2,3, Natsuko Tanabe3,4, Takayuki Kawato2,3✉, Masao Maeno2,3, Noriyoshi Shimizu5,6

1. Nihon University Graduate School of Dentistry, Tokyo, Japan
2. Department of Oral Health Sciences, Nihon University School of Dentistry, Tokyo, Japan
3. Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan
4. Department of Biochemistry, Nihon University School of Dentistry, Tokyo, Japan
5. Department of Orthodontics, Nihon University School of Dentistry, Tokyo, Japan
6. Division of Clinical Research, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan

Abstract

Objective: Matrix metalloproteinases (MMPs), produced by osteoblasts, catalyze the turnover of extracellular matrix (ECM) molecules in osteoid, and the regulation of MMP activity depends on interactions between MMPs and tissue inhibitors of metalloproteinases (TIMPs). We focused on the degradation process of ECM in osteoid that was exposed to mechanical strain, and conducted an in vitro study using MC3T3-E1 osteoblastic cells to examine the effects of tension force (TF) on the expression of MMPs and TIMPs, and activation of mitogen-activated protein kinase (MAPK) pathways.

Design: Cells were incubated on flexible-bottomed culture plates and stimulated with or without cyclic TF for 24 hours. The expression of MMPs and TIMPs was examined at mRNA and protein levels by real-time RT-PCR and Western blotting, respectively. The phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, and stress-activated protein kinases/c-jun N-terminal kinases (SAPK/JNK) were examined by Western blotting.

Results: TF decreased the expression of MMP-1, -3, -13 and phosphorylated ERK1/2. In contrast, TF increased the expression of TIMP-2, -3 and phosphorylated SAPK/JNK. The expression of MMP-2, -14, TIMP-1, -4 and phosphorylated p38 MAPK was unaffected by TF. MMP-1, -3 and -13 expression decreased in cells treated with the ERK inhibitor PD98059 compared with untreated control cells. The JNK inhibitor SP600125 inhibited the TF-induced upregulation of TIMP-2 and -3.

Conclusions: The results suggest that TF suppresses the degradation process that occurs during ECM turnover in osteoid via decreased production of MMP-1, -3 and -13, and increased production of TIMP-2 and -3 through the MAPK signaling pathways in osteoblasts.

Keywords: osteoblast, matrix metalloproteinases, tissue inhibitors of metalloproteinases, mechanical strain, mitogen-activated protein kinase

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How to cite this article:
Karasawa Y, Tanaka H, Nakai K, Tanabe N, Kawato T, Maeno M, Shimizu N. Tension Force Downregulates Matrix Metalloproteinase Expression and Upregulates the Expression of Their Inhibitors through MAPK Signaling Pathways in MC3T3-E1 cells. Int J Med Sci 2015; 12(11):905-913. doi:10.7150/ijms.13263. Available from http://www.medsci.org/v12p0905.htm