title: Mechanically strained cells of the osteoblast lineage organize their extracellular matrix through unique sites of alphavbeta3-integrin expression.
abstract: Bone cells transduce mechanical signals into anabolic biochemical responses. However, the mechanisms of mechanotransduction are unknown. To address this issue, we performed studies in primary cells of the human osteoblast lineage grown on collagen/vitronectin-coated supports. We discovered that mechanical strain stimulated a redistribution of the alphavbeta3-integrin to irregular plaque-like areas at the cell-extracellular matrix surface. Proteins involved in integrin-matrix interactions in focal adhesions, vinculin and talin, did not localize to the plaque-like areas of alphavbeta3-expression, but signaling molecules such as focal adhesion kinase (FAK) did. Mechanical strain increased the number and size of the plaques defined by surface expression of alphavbeta3-integrin. Osteopontin was secreted as a cross-linked macromolecular complex, likely through the action of tissue transglutaminase that also was found in the plaques of alphavbeta3-integrin cell-matrix interaction. Mechanical strain increased mineralization of the extracellular matrix that developed in these plaques in alphavbeta3-integrin-dependent manner. Because the plaque-like areas of cell-matrix interaction exhibit macromolecular assembly and mineralization, we conclude that they may represent subcellular domains of bone formation and that alphavbeta3-integrin activation represents one mechanism by which mechanical strain stimulates bone formation.
authors.affiliation: Department of Internal Medicine, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wozniak
authors.forename: A
authors.initials: A
authors.lastname: Fausto
authors.forename: C P
authors.initials: CP
authors.lastname: Carron
authors.forename: D M
authors.initials: DM
authors.lastname: Meyer
authors.forename: K A
authors.initials: KA
authors.lastname: Hruska
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D010006:Osteoblasts / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D053495:Osteopontin; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D013314:Stress, Mechanical; D011503:Transglutaminases / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
chemical_list: D019030:Receptors, Vitronectin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D019096:Vitronectin; D053495:Osteopontin; D003094:Collagen; D011503:Transglutaminases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human