| 摘要: | 軟骨細胞為軟骨唯一的一種細胞型態，以關節軟骨來說，軟骨覆蓋在硬骨的末端。細胞外間質是一個富含水分的構造，包括膠原蛋白及以玻尿酸為骨架由其他軟骨硫素(chondroitin sulfate)，keratan sulfate和蛋白質分子所構成的聚葡萄糖胺(glycosaminoglycan)。包埋在細胞外間質結構裡的軟骨細胞可以製造新的膠原蛋白和聚葡萄糖胺。在體外培養的實驗中，當軟骨細胞經過連續的分盤培養之後，會漸漸的失去其原有的型態，這個過程稱之為去分化。依據我們實驗室之前的研究，外加第二型膠原蛋白於連續的分盤培養後已漸漸去分化之兔子軟骨細胞，可再度刺激軟骨細胞分泌第二型膠原蛋白及聚葡萄糖胺。在本篇論文的研究中，我們探討外加細胞外間質分子（如：第二型膠原蛋白，玻尿酸或軟骨硫素）是否對人類已去分化的軟骨細胞有相同作用，因此我們於去分化之人類軟骨細胞培養中，以追踪其恢復細胞分化的能力。研究結果證明，細胞外間質分子之第二型膠原蛋白可刺激已去分化之軟骨細胞再度分泌第二型膠原蛋白及聚葡萄糖胺。若外加細胞外間質分子，第二型膠原蛋白，可刺激軟骨細胞再度分化，則此研究成果將可應用於關節炎的治療上。此外，integrins為細胞外間質蛋白質的接受器（如：膠原蛋白，fibronectin，laminins），本論文的另一研究方向為探討細胞外間質物質-第二型膠原蛋白與其接受器integrins結合後所引發的訊息傳遞路徑。我們發現第二型膠原蛋白確定可促使ERK的磷酸化，ERK的磷酸化對於軟骨細胞的分化似乎具有重要的意義。
Chondrocyte is the sole cell type of the cartilage. At the joint, cartilage covers the end of the bone. The extracellular matrix (ECM), a structure of highly hydrated matrix, is consisted of collagen, and glycosaminoglycan (GAG) which is made of hyauronic acid back bone with many other chondroitin sulfate, keratan sulfate and protein components. Chondrocytes are embedded in this ECM structure and produce new collagen and GAGs in cartilage. When chondrocytes are serially expanded, they progressively lose their original phenotype, this process typically described as dedifferentiation. According to previous studies in our laboratory, exogenous type II collagen promoted re-expression of type II collagen mRNA and GAG accumulation in near quiescent rabbit chondrocytes. In this study, we treat human chondrocytes with various exogenous extracellular matrix components (i.e. type II collagen, hyaluronic acid, or chondroitin sulfate). The results demonstrated that exogenous type II collagen indeed induced the re-expression of type II collagen and aggrecan mRNAs, and glycosaminoglycan (GAG) levels. Since exogenous type II collagen indeed make near quiescent chondrocytes re-differentiate, therefore, its preparations maybe be applied to osteoarthritis therapy in the future. In addition, integrins are the principal receptors on animal cells for the most of extracellular matrix proteins ― including collagens, fibronectin, and laminins. Consequently, this study also examined the related signal pathway of integrin. We found that the extracellular signal-regulared protein kinase (ERK) was activated during the induction of the differentiation of dedifferentiated chondrocytes. |
