TSG-6 INTERACTS WITH HYALURONAN AND AGGRECAN IN A PH-DEPENDENT MANNERVIA A COMMON FUNCTIONAL ELEMENT - IMPLICATIONS FOR ITS REGULATION IN INFLAMED CARTILAGE

Cartilage matrix is stabilised by the interactions of proteins with hy aluronan (HA), We compare the pH dependences of HA binding by aggrecan , link protein and TSG-6, Aggrecan and link protein exhibit maximal bi nding 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 show s a dramatic loss of function with increasing pH, TSG-6 also interacts with aggrecan, with a similar pH dependence, and this can be inhibite d 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 dis sociation and that this is regulated by pH gradients in cartilage. (C) 1998 Federation of European Biochemical Societies.