THE FORMATION OF HUMAN SYNOVIAL JOINT CAVITIES - A POSSIBLE ROLE FOR HYALURONAN AND CD44 IN ALTERED INTERZONE COHESION

During fetal development, cavitation occurs within the primitive skele ton along planes destined to become the articular surfaces of synovial joints. A histochemical study of human fetal limbs was undertaken to identify the cell types involved in this cavitation. and the possible role of interactions between cells and extracellular matrix. Cryostat sections were stained with antibodies to CD68, factor VIII related ant igen, prolyl hydroxylase, beta 1 integrin, VCAM-1, proliferating cell nuclear antigen, chondroitin-4 sulphate, chondroitin-6-sulphate, hyalu ronan synthase and CD44. Similar sections were reacted for uridine dip hosphoglucose dehydrogenase (UDPGD) and acid phosphatase activity. Hya luronan was demonstrated using an aggrecan core protein hyaluronan bin ding region probe. Macrophages were present prior to cavitation in the periphery of joint interzones but not at the presumptive joint line i n the central interzone. Fibroblastic cells were present throughout. A bsence of local VCAM-1 expression indicated that cavitation was tempor ally distinct from full fibroblast-like synoviocyte differentiation. C D44 was expressed by interzone cells at all stages. Staining for hyalu ronan and hyaluronan synthase, but not chondroitin sulphates was prese nt in the interzone before and at the time of cavitation. UDPGD activi ty was increased in a narrow band of cells at the presumptive joint li ne prior to cavitation. These findings suggest that joint cavitation i s dependent on the behaviour of fibroblastic cells and/or adjacent cho ndrocytes, rather than macrophages. Since UDPGD activity is involved i n hyaluronan synthesis, it is proposed that joint cavitation is facili tated by a rise in local hyaluronan concentration in an area of tissue where cohesion is dependent on the interaction between cellular CD44 and extracellular hyaluronan. As proposed by Toole et al. (1984) such a local rise in hyaluronan concentration may lead to a switch from int ercellular cohesion to dissociation, leading to tissue cavitation.