| 초록 |
The interaction of human mesenchymal stem cells (hMSCs) with Type I collagen (Col I) matrix plays an important role in regulating their differentiation. We hypothesised that extracellular matrix (ECM) remodelling by matrix metalloproteinases (MMPs) is associated with differentiation of stem cells into specific lineages. We found that expression of MMP13 specifically increased during osteogenic differentiation of hMSCs grown on a Col I matrix. Moreover, knock-down and overexpression of MMP13 reduced and increased osteogenic differentiation, respectively. Unwinding of the Col I matrix by MMP13 promoted osteogenic differentiation of hMSCs and in vivo bone formation by up-regulating expression of RUNX2, integrin α3 and focal adhesion kinase. Furthermore, the transcription factor RUNX2 bound to the MMP13 promoter. These results suggest that remodelling of Col I by MMP13 controls osteogenic differentiation of hMSCs via a MMP13/integrin α3/RUNX2 positive feedback loop. |
