title: Heparan sulfate proteoglycans (HSPGs) modulate BMP2 osteogenic bioactivity in C2C12 cells.
abstract: Cell surface heparan sulfate proteoglycans (HSPGs) have been implicated in bone morphogenetic protein (BMP)-mediated morphogenesis by regulating BMP activity and gradient formation. However, the direct role of HSPGs in BMP signaling is poorly understood. Here we show that HSPGs directly regulate BMP2-mediated transdifferentiation of C2C12 myoblasts into osteoblasts. HSPGs sequester BMP2 at the cell surface and mediate BMP2 internalization. Depletion of cell surface HSPGs by heparinase III treatment or decreased glycosaminoglycan chain sulfation with sodium chlorate enhances BMP2 morpho-genetic bioactivity. The addition of exogenous heparin, a widely used anticoagulant, reduced BMP2 signaling. Our results suggest that cell surface HSPGs mediate BMP2 internalization and modulate BMP2 osteogenic activity.
authors.affiliation: Center For Research in Fibrodysplasia Ossificans Progressiva (FOP) and Related Disorders and the Department of Orthopaedics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Jiao
authors.forename: Paul C
authors.initials: PC
authors.lastname: Billings
authors.forename: Michael P
authors.initials: MP
authors.lastname: O'Connell
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Kaplan
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Shore
authors.forename: David L
authors.initials: DL
authors.lastname: Glaser
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006025:Glycosaminoglycans / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D008565:Membrane Proteins; D016212:Transforming Growth Factor beta; D006493:Heparin; D000469:Alkaline Phosphatase