Regulation of adipogenic differentiation by LAR tyrosine phosphatase in human mesenchymal stem cells and 3T3-L1 preadipocytes

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Title
Regulation of adipogenic differentiation by LAR tyrosine phosphatase in human mesenchymal stem cells and 3T3-L1 preadipocytes
Author(s)
Won Kon-Kim; Hyeyun Jung; Do-Hyung Kim; Eun Young Kim; J W Chung; Yeesook ChoSung Goo ParkByoung Chul Park; Y Ko; Kwang-Hee BaeSang Chul Lee
Bibliographic Citation
Journal of Cell Science, vol. 122, no. 22, pp. 4160-4167
Publication Year
2009
Abstract
Mesenchymal stem cells (MSCs) are multipotent adult stem cells that can differentiate into a variety of mesodermal-lineage cells. MSCs have significant potential in tissue engineering and therapeutic applications; however, the low differentiation and proliferation efficiencies of these cells in the laboratory are fundamental obstacles to their therapeutic use, mainly owing to the lack of information on the detailed signal-transduction mechanisms of differentiation into distinct lineages. With the aid of protein-tyrosine-phosphatase profiling studies, we show that the expression of leukocyte common antigen related (LAR) tyrosine phosphatase is significantly decreased during the early adipogenic stages of MSCs. Knockdown of endogenous LAR induced a dramatic increase in adipogenic differentiation, whereas its overexpression led to decreased adipogenic differentiation in both 3T3-L1 preadipocytes and MSCs. LAR reduces tyrosine phosphorylation of the insulin receptor, in turn leading to decreased phosphorylation of the adaptor protein IRS-1 and its downstream molecule Akt (also known as PKB). We propose that LAR functions as a negative regulator of adipogenesis. Furthermore, our data support the possibility that LAR controls the balance between osteoblast and adipocyte differentiation. Overall, our findings contribute to the clarification of the mechanisms underlying LAR activity in the differentiation of MSCs and suggest that LAR is a candidate target protein for the control of stem-cell differentiation.
Keyword
AdipocyteAdipogenesisLeukocyte common antigenrelatedMesenchymal stem cellsOsteoblastProtein tyrosine phosphatase
ISSN
0021-9533
Publisher
Company Biologists Ltd
DOI
http://dx.doi.org/10.1242/jcs.053009
Type
Article
Appears in Collections:
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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