Heparan and chondroitin sulfate on growth plate perlecan mediate binding and delivery of FGF-2 to FGF receptors

Simone M.L. Smith, Leigh A. West, Prasanthi Govindraj, Xiuqin Zhang, David M. Ornitz, John R. Hassell

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Fibroblast growth factor (FGF)-2 regulates chondrocyte proliferation in the growth plate. Heparan sulfate (HS) proteoglycans bind FGF-2. Perlecan, a heparan sulfate proteoglycan (HSPG) in the developing growth plate, however, contains both HS and chondroitin sulfate (CS) chains. The binding of FGF-2 to perlecan isolated from the growth plate was evaluated using cationic filtration (CAF) and immunoprecipitation (IP) assays. FGF-2 bound to perlecan in both the CAF and IP assays primarily via the HS chains on perlecan. A maximum of 123 molecules of FGF-2 was calculated to bind per molecule of perlecan. When digested with chondroitinase ABC to remove its CS chains, perlecan augmented binding of FGF-2 to the FGFR-1 and FGFR-3 receptors and also increased FGF-2 stimulation of [3H]-thymidine incorporation in BaF3 cells expressing these FGF receptors. These data show that growth plate perlecan binds to FGF-2 by its HS chains but can only deliver FGF-2 to FGF receptors when its CS chains are removed.

Original languageEnglish
Pages (from-to)175-184
Number of pages10
JournalMatrix Biology
Volume26
Issue number3
DOIs
StatePublished - Apr 2007

Keywords

  • Chondrocyte
  • Chondroitin sulfate
  • FGF
  • FGFR
  • Growth plate
  • Heparan sulfate
  • Perlecan

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