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.
| Original language | English |
|---|---|
| Pages (from-to) | 335-340 |
| Number of pages | 6 |
| Journal | Molecules and Cells |
| Volume | 30 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2010 Oct 1 |
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Keywords
- differentiation
- ERK
- LAR tyrosine phosphatase
- osteoblast
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Leukocyte common antigen-related (LAR) tyrosine 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.
In: Molecules and Cells, Vol. 30, No. 4, 01.10.2010, p. 335-340.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Leukocyte common antigen-related (LAR) tyrosine phosphatase positively regulates osteoblast differentiation by modulating extracellular signal-regulated kinase (ERK) activation
AU - Kim, Won Kon
AU - Bae, Kwang Hee
AU - Choi, Hye Ryung
AU - Kim, Do Hyung
AU - Choi, Kwang Soo
AU - Cho, Yee Sook
AU - Kim, Hee Dai
AU - Park, Sung Goo
AU - Park, Byoung Chul
AU - Ko, Yong
AU - Lee, Sang Chul
PY - 2010/10/1
Y1 - 2010/10/1
N2 - 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.
AB - 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.
KW - differentiation
KW - ERK
KW - LAR tyrosine phosphatase
KW - osteoblast
UR - http://www.scopus.com/inward/record.url?scp=78650511385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650511385&partnerID=8YFLogxK
U2 - 10.1007/s10059-010-0123-y
DO - 10.1007/s10059-010-0123-y
M3 - Article
C2 - 20811813
AN - SCOPUS:78650511385
VL - 30
SP - 335
EP - 340
JO - Molecules and Cells
JF - Molecules and Cells
SN - 1016-8478
IS - 4
ER -