alpha 11 beta 1 integrin-mediated MMP-13-dependent collagen lattice contraction by fibroblasts: Evidence for integrin-coordinated collagen proteolysis

作者：Barczyk Malgorzata M; Lu Ning; Popova Svetlana N; Bolstad Anne Isine; Gullberg Donald^*

来源：Journal of Cellular Physiology, 2013, 228(5): 1108-1119.

DOI：10.1002/jcp.24261

We have previously determined that integrin a11 beta 1 is required on mouse periodontal ligament (PDL) fibroblasts to generate the force needed for incisor eruption. As part of the phenotype of a11-/- mice, the incisor PDL (iPDL) is thickened, due to disturbed matrix remodeling. To determine the molecular mechanism behind the disturbed matrix dynamics in the PDL we crossed a11-/- mice with the Immortomouse and isolated immortalized iPDL cells. Microarray analysis of iPDL cells cultured inside a 3D collagen gel demonstrated downregulated expression of a number of genes in a11-deficient iPDL cells, including matrix metalloproteinase-13 (MMP-13) and cathepsin K. a11-/- iPDL cells in vitro displayed disturbed interactions with collagen I during contraction of attached and floating collagen lattices and furthermore displayed reduced MMP-13 protein expression levels. The MMP-13 specific inhibitor WAY 170523 and the Cathepsin K Inhibitor II both blocked part of the a11 integrin-mediated collagen remodeling. In summary, our data demonstrate that in iPDL fibroblasts the mechanical strain generated by a11 beta 1 integrin regulates molecules involved in collagen matrix dynamics. The positive regulation of a11 beta 1-dependent matrix remodeling, involving MMP-13 and cathepsin K, might also occur in other types of fibroblasts and be an important regulatory mechanism for coordinated extracellular and intracellular collagen turnover in tissue homeostasis. J. Cell. Physiol.

• 出版日期2013-5