Osteopontin Deficiency in Rat Vascular Smooth Muscle Cells is Associated with an Inability to Adhere to Collagen and Increased Apoptosis

Department of Pediatrics, The Mount Sinai School of Medicine, New York, New York 10029, USA.
Laboratory Investigation (Impact Factor: 3.68). 12/2000; 80(11):1603-15. DOI: 10.1038/labinvest.3780171
Source: PubMed

ABSTRACT

Osteopontin (OPN) is an extracellular matrix protein that has been implicated in vascular smooth muscle cell (VSMC) adhesion. We have previously described the generation of OPN-deficient VSMC that displayed altered adhesion to collagen. We have examined further the causes and consequences of this altered adhesion. OPN-deficiency was associated with a significant reduction in surface expression of alpha1 and beta1 integrins (mean fluorescence intensity alpha1: OPN-deficient 0.135+/-0.04 vs. control 0.313+/-0.05, p < 0.0001; beta1: OPN-deficient 0.398+/-0.09 vs. control 0.570+/-0.05, p < 0.004). Treatment of normal VSMC with antibody to alpha1 recapitulated the adhesion defect. OPN-deficient cells without collagen exposure had an apoptotic fraction of 1.9%, which increased to 95.7% after 24 hours exposure to collagen. Exogenous OPN added to cultures within 15 minutes of plating restored normal cell adhesion, but did not prevent cells from undergoing apoptosis. Normal VSMC had no detectable apoptosis after 24 hours incubation in suspension, whereas OPN-deficient cells had an apoptotic fraction of 37.5% when incubated in suspension under the same conditions. The data suggest that OPN-deficient VSMC have two distinct abnormalities: an alpha1beta1-mediated inability to adhere normally to collagen and an increased propensity for apoptosis.

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Available from: Andrea S Weintraub, Feb 09, 2015
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    • "SMCs display remarkable plasticity and can undergo changes in phenotype , a process referred to as phenotypic switching, and often exist as a continuum of phenotypes consisting of contractile SMCs which have a complete functional contractile apparatus to the other extreme referred to as proliferating " synthetic " SMCs15161718. Although originally isolated from bone, OPN has been identified in many tissues, including vascular SMCs505152535455565758. OPN is a biomarker of vascular SMC phenotypic switching and is strongly expressed by synthetic SMCs [59], suggesting that we had some degree of synthetic SMC phenotypes present. "
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    • "Additionally, osteopontin-deficient vascular smooth muscle cells show increased apoptosis and decreased adherence. This not only provides further evidence for the role of osteopontin in cellular adherence but also in the inhibition of apoptosis (Weintraub et al, 2000). The mechanism by which osteopontin inhibits apoptosis is thought to be via multiple ligand receptor interactions in response to various proapoptotic signals (Denhardt et al, 2001). "
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