Leukocyte common antigen-related (LAR) tyrosine phosphatase positively regulates osteoblast differentiation by modulating extracellular signal-regulated kinase (ERK) activation

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Title
Leukocyte common antigen-related (LAR) tyrosine phosphatase positively regulates osteoblast differentiation by modulating extracellular signal-regulated kinase (ERK) activation
Author(s)
Won Kon-KimKwang-Hee Bae; Hyeryeong Choi; D H Kim; K S Choi; Yeesook Cho; H D Kim; Sung Goo ParkByoung Chul Park; Y Ko; Sang Chul Lee
Bibliographic Citation
Molecules and Cells, vol. 30, no. 4, pp. 335-340
Publication Year
2010
Abstract
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.
Keyword
differentiationERKLAR tyrosine phosphataseosteoblast
ISSN
1016-8478
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.1007/s10059-010-0123-y
Type
Article
Appears in Collections:
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
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