title: Circulating fibronectin affects bone matrix, whereas osteoblast fibronectin modulates osteoblast function.
abstract: The bone matrix is composed mostly of collagen, but the initial and continuous presence of fibronectin was found to be crucial for collagen matrix integrity in vitro. It has been assumed that osteoblasts produce the fibronectin required for bone matrix formation. Using transgenic mice, we conditionally deleted fibronectin in the osteoblasts and in the liver using the cre-loxP system. We also used mice with mutated fibronectin and conditionally deleted beta(1)-integrin in osteoblasts to identify the receptor involved in fibronectin effects on osteoblasts. Conditional deletion of fibronectin in the differentiating osteoblasts [using the 2.3 kb collagen-alpha1(I) promoter] failed to show a decrease in fibronectin amount in the bone matrix despite evidence of successful deletion. Using these mice we established that osteoblast-derived fibronectin solely affects osteoblast function. This effect was not mediated by integrins that bind to the RGD motif. Conditional deletion of fibronectin in the liver showed a marked decrease in fibronectin content in the matrix associated with decreased mineral-to-matrix ratio and changed biomechanical properties but had no effect on osteoblasts or osteoclasts. In conclusion, osteoblast fibronectin affects osteoblasts function. This does not seem to be mediated by the RGD motif on fibronectin. In contrast, liver-derived fibronectin affects bone matrix properties without affecting osteoblast or osteoclast function. A novel role for liver-derived circulating fibronectin thus was defined and delineated from that of locally produced fibronectin.
authors.affiliation: Max-Planck Institute for Biochemistry, 82152 Martinsried, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Bentmann
authors.forename: Nina
authors.initials: N
authors.lastname: Kawelke
authors.forename: David
authors.initials: D
authors.lastname: Moss
authors.forename: Hanswalter
authors.initials: H
authors.lastname: Zentgraf
authors.forename: Yohann
authors.initials: Y
authors.lastname: Bala
authors.forename: Irina
authors.initials: I
authors.lastname: Berger
authors.forename: Juerg A
authors.initials: JA
authors.lastname: Gasser
authors.forename: Inaam A
authors.initials: IA
authors.lastname: Nakchbandi
mesh_terms: D000818:Animals; D015519:Bone Density; D001857:Bone Matrix / Q000378:metabolism*; D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D003094:Collagen