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Fibronectin is a survival factor for differentiated osteoblastsThe skeletal extracellular matrix produced by osteoblasts contains the glycoprotein fibronectin, which regulates the adhesion, differentiation and function of various adherent cells. Interactions with fibronectin are required for osteoblast differentiation in vitro, since fibronectin antagonists added to cultures of immature fetal calvarial osteoblasts inhibit their progressive differentiation. To determine if fibronectin plays a unique role in fully differentiated osteoblasts, cultures that had already formed mineralized nodules in vitro were treated with fibronectin antagonists. Fibronectin antibodies caused >95% of the cells in the mature cultures to display characteristic features of apoptosis (nuclear condensation, apoptotic body formation, DNA laddering) within 24 hours. Cells appeared to acquire sensitivity to fibronectin antibody-induced apoptosis as a consequence of differentiation, since antibodies failed to kill immature cells and the first cells killed were those associated with mature nodules. Intact plasma fibronectin, as well as fragments corresponding to the amino-terminal, cell-binding, and carboxy-terminal domains of fibronectin, independently induced apoptosis of mature (day-13), but not immature (day-4), osteoblasts. Finally, transforming growth factor-beta1 partially protected cells from the apoptotic effects of fibronectin antagonists. Thus, in the course of maturation cultured osteoblasts switch from depending on fibronectin for differentiation to depending on fibronectin for survival. These data suggest that fibronectin, together with transforming growth factor-beta1, may affect bone formation, in part by regulating the survival of osteoblasts.
Document ID
20040172716
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Globus, R. K.
(NASA Ames Research Center Moffett Field, CA United States)
Doty, S. B.
Lull, J. C.
Holmuhamedov, E.
Humphries, M. J.
Damsky, C. H.
Date Acquired
August 22, 2013
Publication Date
May 1, 1998
Publication Information
Publication: Journal of cell science
Volume: 111 ( Pt 10)
ISSN: 0021-9533
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: DE-07204
CONTRACT_GRANT: DE-10306
Distribution Limits
Public
Copyright
Other
Keywords
NASA Center ARC
NASA Discipline Musculoskeletal

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