軟骨コラーゲン遺伝子の発現制御機構(<特集>コラーゲン研究)

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Cartilage is a highly specialized tissue and serves as the template for the growth and development of most bones. Cartilage development is initiated by mesenchymal cell condensation followed by a series of chondrocyte maturation processes including resting, proliferative, and hypertrophic chondrocytes. Cartilage contains an extensive extracellular matrix which includes type II, IX, X and XI collagens, and provides mechanical strength to resist compression in joints. The type II collagen forms collagen fibrils and provides a structural framework for cartilage matrix. Type XI collagen co-assembles stoichiometrically with type II collagen in the fibrils, whereas the type IX collagen is associated with the surface of the fibrils. Type X collagen is predominantly expressed in hypertrophic chondrocytes. Type II collagen, a homotrimer of the al (II) chain (Col2a1),is a major extracellular matrix protein in cartilage. Type II collagen is synthesized primarily by proliferating chondrocytes but not by hypertrophic chondrocytes. The type XI collagen molecule is composed of three subunits: al (XI), α2 (XI), and α3 (XI). The α3 (XI) chain is a posttranslational variant of the al (II) chain, whereas the al (XI) and α2 (XI) chains are distinct gene products. Expression of α2 (XI) chains (Collla2) appears to be predominantly restricted to cartilage. Disruption of the expression of these collagen genes leads to degenerative joint disorders and a variety of chondrodysplasias, suggesting that fidelity of the cartilage-specific collagen expression is essential for maintaining normal cartilage structure and function. Recently, transcriptional regulation of Col2a1 and Col11a2 have been intensivly analyzed. It is mediated by tissue-specific regulatory elements located within the promoter and first intron. Recent reports suggest that SOX 9, a member of the transcription factor family with an HMG-type DNA binding domain homologous to that of SRY, plays an important role in chondrocyte differentiation and cartilage formation. Mutations in the gene for SOX 9 cause campomelic dysplasia, a severe dwarfism syndrome, which affects all cartilage-derived structures. SOX 9 binds as a complex with L-SOX 5 and SOX 6 to an HMG-box-like sequences in the enhancers and/or promoters of the collagen genes, and upregulates the cartilage specific activities. On the other hand, we have found that zinc-finger transcription factors CRYBP 1 and EPM 315 negatively regulate the tissue specific expression of Col2a1 and Col11a2, respectively. In this review, we discussed about the positive and negative regulations of transcription of cartilage-specific collagen genes.
日本結合組織学会の論文
2002-06-25

軟骨コラーゲン遺伝子の発現制御機構(<特集>コラーゲン研究)

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