Type IIA procollagen: Expression in developing chicken limb cartilage and human osteoarthritic articular cartilage

Type IIA procollagen is an alternatively spliced product of the type II col lagen gene and uniquely contains the cysteine (cys)-rich lobular domain in its amino (N)-propeptide. To understand the function of type IIA procollage n in cartilage development under normal and pathologic conditions, the deta iled expression pattern of type IIA procollagen was determined in progressi ve stages of development in embryonic chicken limb cartilages (days 5-19) a nd in human adult articular cartilage. Utilizing the antibodies specific fo r the cys-rich domain of the type IIA procollagen N-propeptide, we localize d type IIA procollagen in the pericellular and interterritorial matrix of c ondensing pre-chondrogenic mesenchyme (day 5) and early cartilage (days 7-9 ). The intensity of immunostaining was gradually lost with cartilage develo pment, and staining became restricted to the inner layer of perichondrium a nd the articular cap (day 12). Later in development, type IIA procollagen w as re-expressed at the onset of cartilage hypertrophy (day 19). Different f rom type X collagen, which is expressed throughout hypertrophic cartilage, type IIA procollagen expression was transient and restricted to the zone of early hypertrophy, Immunoelectron microscopic and immunoblot analyses show ed that a sig nificant amount of the type IIA procollagen N-propeptide, but not the carboxyl (C)-propeptide, was retained in matrix collagen fibrils o f embryonic limb cartilage. This suggests that the type IIA procollagen N-p ropeptide plays previously unrecognized roles in fibrillogenesis and chondr ogenesis. We did not detect type IIA procollagen in healthy human adult art icular cartilage. Expression of type IIA procollagen, together with that of type X collagen, was activated by articular chondrocytes in the upper zone of moderately and severely affected human osteoarthritic cartilage, sugges ting that articular chondrocytes, which normally maintain a stable phenotyp e, undergo hypertrophic changes in osteoarthritic cartilage. Based on our d ata, we propose that type IIA procollagen plays a significant role in chond rocyte differentiation and hypertrophy during normal cartilage development as well as in the pathogenesis of osteoarthritis. (C) 2001 Wiley-Liss, Inc.