title: TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a common functional element: implications for its regulation in inflamed cartilage.
abstract: Cartilage matrix is stabilised by the interactions of proteins with hyaluronan (HA). We compare the pH dependences of HA binding by aggrecan, link protein and TSG-6. Aggrecan and link protein exhibit maximal binding across a wide pH range (6.0-8.0). TSG-6, a protein that is only produced during inflammation, binds maximally at about pH 6.0 but shows a dramatic loss of function with increasing pH. TSG-6 also interacts with aggrecan, with a similar pH dependence, and this can be inhibited by HA. Thus, a common binding surface on TSG-6 may be involved in HA and aggrecan binding. We propose that TSG-6 is involved in matrix dissociation and that this is regulated by pH gradients in cartilage.
authors.affiliation: Department of Biochemistry, University of Oxford, UK.
authors.forename: A A
authors.initials: AA
authors.lastname: Parkar
authors.forename: J D
authors.initials: JD
authors.lastname: Kahmann
authors.forename: S L
authors.initials: SL
authors.lastname: Howat
authors.forename: M T
authors.initials: MT
authors.lastname: Bayliss
authors.forename: A J
authors.initials: AJ
authors.lastname: Day
mesh_terms: D053674:Aggrecans; D001665:Binding Sites; D002356:Cartilage / Q000502:physiology / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007249:Inflammation; D007700:Kinetics; D037181:Lectins, C-Type; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011509:Proteoglycans / Q000378:metabolism*
chemical_list: D053674:Aggrecans; D015815:Cell Adhesion Molecules; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; C072273:TNFAIP6 protein, human; D006820:Hyaluronic Acid