Osteoactivin Promotes Osteoblast Adhesion Through HSPG and αvβ1 Integrin

Authors

  • Fouad M. Moussa,

    1. Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio
    2. School of Biomedical Sciences, Kent State University, Kent, Ohio
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  • Israel Arango Hisijara,

    1. Department of Anatomy and Cell Biology, Temple University, Philadelphia, Pennsylvania
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  • Gregory R. Sondag,

    1. Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio
    2. School of Biomedical Sciences, Kent State University, Kent, Ohio
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  • Ethan M. Scott,

    1. Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio
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  • Nagat Frara,

    1. Department of Anatomy and Cell Biology, Temple University, Philadelphia, Pennsylvania
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  • Samir M. Abdelmagid,

    1. Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio
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  • Fayez F. Safadi

    Corresponding author
    1. Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio
    2. School of Biomedical Sciences, Kent State University, Kent, Ohio
    • Correspondence to: Fayez Safadi, PhD, Department of Anatomy and Neurobiology, Northeast Ohio Medical University, 4209 State Rt. 44, Rootstown, OH 44224. E-mail: fayez.safadi@neomed.edu

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ABSTRACT

Osteoactivin (OA), also known as glycoprotein nmb (gpnmb) plays an important role in the regulation of osteoblast differentiation and function. OA induced osteoblast differentiation and function in vitro by stimulating alkaline phosphatase (ALP) activity, osteocalcin production, nodule formation, and matrix mineralization. Recent studies reported a role for OA in cell adhesion and integrin binding. In this study, we demonstrate that recombinant osteoactivin (rOA) as a matricellular protein stimulated adhesion, spreading and differentiation of MC3T3-E1 osteoblast-like cells through binding to αvβ1 integrin and heparan sulfated proteoglycans (HSPGs). MC3T3-E1 cell adhesion to rOA was blocked by neutralizing anti-OA or anti-αv and β1 integrin antibodies. rOA stimulated-osteoblast adhesion was also inhibited by soluble heparin and sodium chlorate. Interestingly, rOA stimulated-osteoblast adhesion promoted an increase in FAK and ERK activation, resulting in the formation of focal adhesions, cell spreading and enhanced actin cytoskeleton organization. In addition, differentiation of primary osteoblasts was augmented on rOA coated-wells marked by increased alkaline phosphatase staining and activity. Taken together, these data implicate OA as a matricellular protein that stimulates osteoblast adhesion through binding to αvβ1 integrin and cell surface HSPGs, resulting in increased cell spreading, actin reorganization, and osteoblast differentiation with emphasis on the positive role of OA in osteogenesis. J. Cell. Biochem. 115: 1243–1253, 2014. © 2014 Wiley Periodicals, Inc.

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