The formation of human synovial joint cavities: a possible role for hyaluronan and CD44 in altered interzone cohesion

Abstract

During fetal development, cavitation occurs within the primitive skeleton 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 antigen, prolyl hydroxylase, beta 1 integrin, VCAM-1, proliferating cell nuclear antigen, chondroitin-4 sulphate, chondroitin-6-sulphate, hyaluronan synthase and CD44. Similar sections were reacted for uridine diphosphoglucose dehydrogenase (UDPGD) and acid phosphatase activity. Hyaluronan was demonstrated using an aggrecan core protein hyaluronan binding region probe. Macrophages were present prior to cavitation in the periphery of joint interzones but not at the presumptive joint line in the central interzone. Fibroblastic cells were present throughout. Absence of local VCAM-1 expression indicated that cavitation was temporally distinct from full fibroblast-like synoviocyte differentiation. CD44 was expressed by interzone cells at all stages. Staining for hyaluronan and hyaluronan synthase, but not chondroitin sulphates was present in the interzone before and at the time of cavitation. UDPGD activity was increased in a narrow band of cells at the presumptive joint line prior to cavitation. These findings suggest that joint cavitation is dependent on the behaviour of fibroblastic cells and/or adjacent chondrocytes, rather than macrophages. Since UDPGD activity is involved in hyaluronan synthesis, it is proposed that joint cavitation is facilitated 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 intercellular cohesion to dissociation, leading to tissue cavitation.