Leukocyte Common Antigen-Related (LAR) Tyrosine Phosphatase Positively Regulates Osteoblast Differentiation by Modulating Extracellular Signal-Regulated Kinase (ERK) Activation
Leukocyte Common Antigen-Related (LAR) Tyrosine Phosphatase Positively Regulates Osteoblast Differentiation by Modulating Extracellular Signal-Regulated Kinase (ERK) Activation
- 주제(키워드) differentiation , ERK , LAR tyrosine phosphatase , osteoblast
- 발행기관 한국분자세포생물학회
- 발행년도 2010
- 총서유형 Journal
- UCI G704-000079.2010.30.4.003
- KCI ID ART001493941
- 본문언어 영어
초록/요약
Protein tyrosine phosphatases (PTPs) are pivotal regula-tors of key cellular functions, including cell growth, differ-entiation, and adhesion. Previously, we reported that leu-kocyte common antigen-related (LAR) tyrosine phos-phatase promotes osteoblast differentiation in MC3T3-E1 preosteoblast cells. In the present study, the mechanism of the regulatory action of LAR on osteoblast differentia-tion 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) activa-tion during osteoblast differentiation. In contrast, a mar-ginal 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 func-tions 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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