期刊
EXPERIMENTAL CELL RESEARCH
卷 314, 期 4, 页码 763-773出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2007.12.007
关键词
LG domain; osteogenesis; laminin-332; mesenchymal stem cell; osterix; extracellular matrix
资金
- NCI NIH HHS [T32 CA009592] Funding Source: Medline
- NIBIB NIH HHS [1R01EB002197, R01 EB002197, R01 EB002197-03, R01 EB002197-04] Funding Source: Medline
The overall mechanisms governing the role of laminins during osteogenic differentiation of human mesenchymal stem cells (hMSC) are poorly understood. We previously reported that laminin-332 induces an osteogenic phenotype in hMSC and does so through a focal adhesion kinase (FAK) and extracellular signal-related kinase (ERK) dependent pathway. We hypothesized that this is a result of integrin-ECM binding, and that it occurs via the known alpha 3 LG3 integrin binding domain of laminin-332. To test this hypothesis we cultured hMSC on several different globular domains of laminin-332. hMSC adhered best to the LG3 domain, and this adhesion maximally activated FAK and ERK within 120 min. Prolonged culturing (8 or 16 days) of hMSC on LG3 led to activation of the osteogenic transcription factor Runx2 and expression of key osteogenic markers (osterix, bone sialoprotein 2, osteocalcin, alkaline phosphatase, extracellular calcium) in hMSC. LG3 domain binding did not increase matrix mineralization, demonstrating that the LG3 domain alone is not sufficient to induce complete osteogenic differentiation in vitro. We conclude that the LG3 domain mediates attachment of hMSC to laminin-332 and that this adhesion recapitulates most, but not all, of the osteogenic differentiation associated with laminin-5 binding to hMSC. (C) 2007 Elsevier Inc. All rights reserved.
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