Leukocyte common antigen-related (LAR) tyrosine phosphatase positively regulates osteoblast differentiation by modulating extracellular signal-regulated kinase (ERK) activation |
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Authors: | Won Kon Kim Kwang-Hee Bae Hye-Ryung Choi Do-Hyung Kim Kwang-Soo Choi Yee Sook Cho Hee Dai Kim Sung Goo Park Byoung Chul Park Yong Ko Sang Chul Lee |
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Institution: | 1. Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea 2. Division of Life Science and Genetic Engineering, College of Life and Environmental Sciences, Korea University, Seoul, 136-701, Korea 3. Department of Health Service Management, Woosuk University, Jeonju, 565-701, Korea 4. Development and Differentiation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea 5. Department of Biotechnology and Biomedicine, Chungbuk Provincial University, Okchon, 373-806, Korea
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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. |
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