Laminin-5 induces osteogenic gene expression in human mesenchymal stem cells through an ERK-dependent pathway

Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180-3596, USA.
Molecular Biology of the Cell (Impact Factor: 4.47). 03/2005; 16(2):881-90. DOI: 10.1091/mbc.E04-08-0695
Source: PubMed


The laminin family of proteins is critical for managing a variety of cellular activities including migration, adhesion, and differentiation. In bone, the roles of laminins in controlling osteogenic differentiation of human mesenchymal stem cells (hMSC) are unknown. We report here that laminin-5 is found in bone and expressed by hMSC. hMSC isolated from bone synthesize laminin-5 and adhere to exogenous laminin-5 through alpha3beta1 integrin. Adhesion to laminin-5 activates extracellular signal-related kinase (ERK) within 30 min and leads to phosphorylation of the osteogenic transcription factor Runx2/CBFA-1 within 8 d. Cells plated on laminin-5 for 16 d express increased levels of osteogenic marker genes, and those plated for 21 d deposit a mineralized matrix, indicative of osteogenic differentiation. Addition of the ERK inhibitor PD98059 mitigates these effects. We conclude that contact with laminin-5 is sufficient to activate ERK and to stimulate osteogenic differentiation in hMSC.

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Available from: Adele L Boskey
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    • "To investigate the effect of ECM components on hMSCs behavior, a range of proteins, including fibronectin (FN, 40 μg/ml), laminin (LN, 40 μg/ml) and osteocalcin (OCN, 20 μg/ml & 40 μg/ml) were entrapped within the GE hydrogels (Figure b). The selected proteins are well known for their roles in osteogenic differentiation of hMSCs333435363738 and their affinity towards collagen I and IV394041, from which GE is derived. We also examined the effects of growth factors, using bone morphogenic proteins, (BMP2 and & BMP5, 50 ng/ml), which promote osteogenesis via the hedgehog pathway42. "
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