Role of proteoglycan in the provisional calcification of cartilage. A review and reinterpretation

Study of the calcification of cartilage in endochondral ossification has yielded two apparently contradictory views of the role of proteoglycan in this process. The ability of proteoglycan to act as a calcium-concentrating agent (Kalksalzfänger) in cartilage is consistent with the view that proteoglycans are promoters of calcification. However, study of their effect on hydroxyapatite formation in vitro suggests that proteoglycans are inhibitors of cartilage calcification. A resolution of this paradox is now proposed. Proteoglycans inhibit hydroxyapatite formation under in vitro conditions of limited calcium availability (in part) by binding calcium ions. However, under in vivo conditions of essentially infinite calcium availability, proteoglycans may promote hydroxyapatite formation, since binding of calcium to proteoglycan will not decrease the free calcium concentration, and the bound calcium may easily be displaced. Therefore, it is proposed that the role of proteoglycans in the calcification of cartilage is to function as a cation-exchanging calcium reservoir.