Protein tyrosine phosphatases (PTPs) are pivotal regulators of key cellular functions, including cell growth, differentiation, and adhesion. Previously, we reported that leukocyte common antigen-related (LAR) tyrosine phosphatase promotes osteoblast differentiation in MC3T3-E1 preosteoblast cells. In the present study, the mechanism of the regulatory action of LAR on osteoblast differentiation was investigated. The mineralization of extracellular matrix and calcium accumulation in MC3T3-E1 cells were markedly enhanced by LAR overexpression, and these effects were further increased by treatment with a MEK inhibitor. In addition, LAR overexpression dramatically reduced extracellular signal-regulated kinase (Erk) activation during osteoblast differentiation. In contrast, a marginal effect of the inactive LAR mutant on Erk activation was detected. Expression of osteoblast-related genes such as ALP, BSP, DLX5, OCN, and RUNX2, was increased by LAR overexpression during osteoblast differentiation. On the basis of these results, we propose that LAR functions as a positive regulator of osteoblast differentiation by modulating ERK activation. Therefore, LAR phosphatase could be used as a novel regulatory target protein in many bone-associated diseases, including osteoporosis.
Bibliographical noteFunding Information:
We thank Drs. Do Hee Lee, Sayeon Cho and Sang J. Chung for careful reading of the manuscript and helpful advice. This work was supported by grants from Korea Research Institute of Bioscience and Biotechnology Open Innovation Program (to K. - H. Bae), Korea Research Council of Fundamental Science and Technology (to Y.S. Cho), and Stem Cell Research Program of Korea Research Foundation (to S.C. Lee), Korea.
- LAR tyrosine phosphatase
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology