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

Abstract

Type IIA procollagen is an alternatively spliced product of the type II collagen gene and uniquely contains the cysteine (cys)-rich globular domain in its amino (N)-propeptide. To understand the function of type IIA procollagen in cartilage development under normal and pathologic conditions, the detailed expression pattern of type IIA procollagen was determined in progressive stages of development in embryonic chicken limb cartilages (days 5-19) and in human adult articular cartilage. Utilizing the antibodies specific for the cys-rich domain of the type IIA procollagen N-propeptide, we localized type IIA procollagen in the pericellular and interterritorial matrix of condensing prechondrogenic mesenchyme (day 5) and early cartilage (days 7-9). The intensity of immunostaining was gradually lost with cartilage development, and staining became restricted to the inner layer of perichondrium and the articular cap (day 12). Later in development, type IIA procollagen was re-expressed at the onset of cartilage hypertrophy (day 19). Different from 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 showed that a significant amount of the type IIA procollagen N-propeptide, but not the carboxyl (C)-propeptide, was retained in matrix collagen fibrils of embryonic limb cartilage. This suggests that the type IIA procollagen N-propeptide plays previously unrecognized roles in fibrillogenesis and chondrogenesis. We did not detect type IIA procollagen in healthy human adult articular 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, suggesting that articular chondrocytes, which normally maintain a stable phenotype, undergo hypertrophic changes in osteoarthritic cartilage. Based on our data, we propose that type IIA procollagen plays a significant role in chondrocyte differentiation and hypertrophy during normal cartilage development as well as in the pathogenesis of osteoarthritis.

Activin A induces craniofacial cartilage from undifferentiated Xenopus ectoderm in vitro

“…The Col2 mRNA expression increased in the explants to a maximum level from day 4 to 7 of culture and then decreased from day 10. The result above is consistent with a decrease in Col2 mRNA expression when chondrocytes differentiate to the hypertrophic level (27,28). Immunohistochemical examination revealed barely detectable levels of Col2 protein in the mature chondrocytes, and its localization was restricted to the perichondrium in the 14 day-cultured explants, as was the case in embryos.…”

Differences in metabolic parameters and gene expression related to Osteochondrosis/Osteoarthrosis in pigs fed 25-hydroxyvitamin D3

“…The changes in gene expression that were observed in the present study seem to indicate that there may be similarities between the molecular changes that occur in OC/OA in pigs and degenerative changes in the articular cartilage of other mammals in osteoarthrosis or osteoarthritis. The expression of both collagen types II and X is altered in osteoarthritic/osteoarthrotic articular cartilage, with type II being down regulated or degraded [27,42] and type X upregulated [11,30], respectively. There is also evidence that the changes in mRNA levels observed in the present study may lead to alterations in the abundance of collagen proteins within the extracellular matrix.…”

Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis

“…On the one hand, type IIB procollagen is expressed at high levels in well-differentiated chondrocytes, forming the framework of normal adult cartilage. On the other hand, type IIA procollagen is temporally expressed in prechondrogenic condensing limb mesenchyme, sclerotome, and early cartilage (17)(18)(19)(20) and can be reexpressed later in development at the onset of cartilage hypertrophy (21). In addition, it has recently been shown that type IIA procollagen is re-expressed by adult articular chondrocytes of affected human OA cartilage (21,22).…”

“…On the other hand, type IIA procollagen is temporally expressed in prechondrogenic condensing limb mesenchyme, sclerotome, and early cartilage (17)(18)(19)(20) and can be reexpressed later in development at the onset of cartilage hypertrophy (21). In addition, it has recently been shown that type IIA procollagen is re-expressed by adult articular chondrocytes of affected human OA cartilage (21,22). During secretion and before incorporation of type II collagen molecules into cartilage matrix, the Nand C-propeptides are removed by specific enzymes and released in part into the synovial fluid and cleared into the blood.…”