z-logo
Premium
Heparan and chondroitin sulfate modifications in signaling pathways regulating articular cartilage homeostasis
Author(s) -
Randell Rachel Leigh,
Wittmeyer Richard,
Selva Erica M
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.695.8
Subject(s) - microbiology and biotechnology , chondroitin sulfate , aggrecan , perlecan , cartilage , decapentaplegic , patched , signal transduction , chemistry , extracellular matrix , morphogen , proteoglycan , chondrocyte , osteoarthritis , hedgehog , biology , biochemistry , mutant , anatomy , medicine , glycosaminoglycan , pathology , imaginal disc , alternative medicine , gene , articular cartilage
Degradation of articular cartilage leads to osteoarthritis (OA) in humans. Articular cartilage homeostasis depends on signaling events modulated by extracellular matrix glycoproteins. We tested the hypothesis that disrupting heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans would alter signaling pathways relevant to cartilage homeostasis. Mosaic mutant and wild‐type Drosophila wing discs were used to visualize the effects of mutations in two genes: O‐xylosyltransferase ( oxt ), required for linking HS and CS to core proteins, and sulfateless ( sfl ), essential for decorating HS with negatively charged sulfate groups. We performed immunostaining of signaling ligands and pathway activation targets, including: Decapentaplegic, the homolog of human Bone Morphogenic Protein involved in anabolic cartilage processes; Wingless, the homolog of human Wnts implicated in cartilage repair; and Hedgehog and its receptor Patched. We demonstrate the importance of HS and CS for proper activation and movement of signaling molecules. Surprisingly, sfl appears to be more disruptive than oxt on signaling. Ongoing experiments examine the role of the core proteoglycan Dally‐like and look for signals that might upregulate cartilage deposition. These results will help to identify targets for the development of novel OA therapeutics.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here