title: Matrix metalloproteinase activity synergizes with alpha2beta1 integrins to enhance collagen remodeling.
abstract: Cell-matrix interactions transmit a wealth of information about the extracellular environment. In return, a variety of responses from the cell are initiated by changes in the matrix. One such response involves the positive regulation of matrix metalloproteinases (MMPs) by alpha2beta1 integrin attaching to a specific extracellular matrix component, collagen. This study explores the relationship between mechanical and biochemical functions of alpha2beta1 integrins as it pertains to regulating matrix remodeling. To understand this relationship, the individual influences of MMP activity and alpha2beta1 integrin function on collagen gel contraction were studied. We have observed little evidence of mutual participation in matrix remodeling by the alpha2beta1 integrin and MMP activity in cell models where alpha2 is minimally expressed. In cells expressing high levels of alpha2, we see an increase in gel contraction that is enhanced by MMP activity. Measuring tension as it builds within the gel reveals that alpha2beta1 integrin presence correlates with force output but is insensitive to MMP activity. These data strongly suggest that alpha2beta1 regulates collagen gel remodeling through multiple simultaneous mechanisms including force generation and modulation of MMP activity.
authors.affiliation: University of Massachusetts, Graduate School of Biomedical Sciences, Worcester, MA 02125, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Phillips
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Bonassar
mesh_terms: D016723:Bone Remodeling; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism*; D018076:DNA, Complementary / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D038982:Integrin alpha2beta1; D003094:Collagen; D020782:Matrix Metalloproteinases