title: Syndecan-3: a cell-surface heparan sulfate proteoglycan important for chondrocyte proliferation and function during limb skeletogenesis.
abstract: Syndecans are single-pass integral membrane components that serve as co-receptors for growth factors and cytokines and can elicit signal transduction via their cytoplasmic tails. We review here previous studies from our groups on syndecan-3 biology and function in the growth plates of developing long bones in chick and mouse embryos. Gain- and loss-of-function data indicate that syndecan-3 has important roles in restricting mitotic activity to the proliferative zone of growth plate and may do so in close cooperation and interaction with the signaling molecule Indian hedgehog (IHH). Biochemical and protein-modeling data suggest a dimeric/oligomeric syndecan-3 configuration on the chondrocyte's cell surface. Analyses of embryos misexpressing syndecan-3 or lacking IHH provide further clues on syndecan-3/IHH interdependence and interrelationships. The data and the conclusions reached provide insights into mechanisms fine-tuning chondrocyte proliferation, maturation, and function in the developing and growing skeleton and into how abnormalities in these fundamental mechanisms may subtend human congenital pathologies, including osteochondromas in hereditary multiple exostoses syndrome.
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University College of Medicine, Philadelphia, PA 19107, USA. maurizio.pacifici@jefferson.edu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pacifici
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimo
authors.forename: Chiara
authors.initials: C
authors.lastname: Gentili
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kirsch
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Freeman
authors.forename: Motomi
authors.initials: M
authors.lastname: Enomoto-Iwamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwamoto
authors.forename: Eiki
authors.initials: E
authors.lastname: Koyama
mesh_terms: D000818:Animals; D001846:Bone Development; D049109:Cell Proliferation; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology*; D005121:Extremities / Q000196:embryology* / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D011509:Proteoglycans / Q000502:physiology*; D053670:Syndecan-3
chemical_list: D006133:Growth Substances; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508301:SDC3 protein, human; C508302:Sdc3 protein, mouse; D053670:Syndecan-3