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

Won Kon Kim, Hyeyun Jung, Do Hyung Kim, Eun Young Kim, Jin Woong Chung, Yee Sook Cho, Sung Goo Park, Byoung Chul Park, Yong Ko, Kwang Hee Bae, Sang Chul Lee

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43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4160-4167
Number of pages8
JournalJournal of Cell Science
Volume122
Issue number22
DOIs
Publication statusPublished - 2009 Nov 15

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Keywords

  • Adipocyte
  • Adipogenesis
  • Leukocyte common antigenrelated
  • Mesenchymal stem cells
  • Osteoblast
  • Protein tyrosine phosphatase

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kim, W. K., Jung, H., Kim, D. H., Kim, E. Y., Chung, J. W., Cho, Y. S., Park, S. G., Park, B. C., Ko, Y., Bae, K. H., & Lee, S. C. (2009). Regulation of adipogenic differentiation by LAR tyrosine phosphatase in human mesenchymal stem cells and 3T3-L1 preadipocytes. Journal of Cell Science, 122(22), 4160-4167. https://doi.org/10.1242/jcs.053009