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

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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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.

Original languageEnglish
Pages (from-to)335-340
Number of pages6
JournalMolecules and cells
Issue number4
Publication statusPublished - 2010 Oct 1



  • ERK
  • LAR tyrosine phosphatase
  • differentiation
  • osteoblast

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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