Matrix biology

Paper evaluated in Faculty 1000

α11β1 integrin-mediated MMP-13-dependent collagen lattice contraction by fibroblasts: evidence for integrin-coordinated collagen proteolysis.

Main content

Barczyk MM, Lu N, Popova SN, Bolstad AI, Gullberg D. J Cell Physiol. 2013 May; 228(5):1108-19

Evaluated by Thomas Pap and Ulrich König

Technical Advance

DOI: 10.3410/f.717960463.793486764

Barczyk et al. investigate α11β1 as a major matrix remodeling receptor on cultured periodontal ligament (PDL) fibroblasts. This paper shows that genes related to matrix dynamics are downregulated in α11-I- incisor PDL (iPDL) cells.

In vitro, a knockdown of α11 resulted in a reduced ability of matrix remodeling as shown in gel contraction experiments. To examine the effect of α11 levels on the ability of incisor fibroblasts to interact with collagen I, the authors analyzed the ability of cells to reorganize collagen in floating and attached collagen lattices. The effect of active collagen remodeling was seen as an extrusion of culture medium from the gel.

In order to understand the mechanism underlying the in vivo PDL phenotype of α11-deficient mice, the authors placed iPDL cells in the 3D attached collagen gels and for further analyses they chose the five top-regulated genes (Glypican-3, Advillin, interleukin-I like receptor I, MMP-13 and cathepsin K) with highest fold change in gene expression and confirmed by using microarrays that the validated genes only displayed either very low or no detectable expression in the α11-I- samples compared with corresponding α11+I+ samples. Further analyses show that α11β1 regulates MMP-13 levels inside a 3D collagen gel and that the α11β1-mediated collagen reorganization depends on MMP-13 and cathepsin K activity.