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KMID : 0578320100300040335
Molecules and Cells
2010 Volume.30 No. 4 p.335 ~ p.340
Leukocyte Common Antigen-Related (LAR) Tyro-sine Phosphatase Positively Regulates Osteoblast Differentiation by Modulating Extracellular Signal-Regulated Kinase (ERK) Activation
Kim Won-Kon

Bae Kwang-Hee
Choi Hye-Ryung
Kim Do-Hyung
Choi Kwang-Soo
Cho Yee-Sook
Kim Hee-Dai
Park Sung-Goo
Park Byoung-Chul
Ko Yong
Lee Sang-Chul
Abstract
Protein tyrosine phosphatases (PTPs) are pivotal regula-tors of key cellular functions, including cell growth, diffe-rentiation, 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 an 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 overex-pression 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
differentiation, ERK, LAR tyrosine phosphatase, osteoblast
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