| Summary: | 碩士 === 臺北醫學大學 === 生物醫學材料研究所 === 96 === The cartilage extracellular matrix (ECM) contains large amount of glycosaminoglycan (GAG), which has water-holding property, contributes resilience and resistance to joint deformation. The most common GAG including chondroitin sulfate (CS), keratan sulfate (KS), and heparan sulfate (HS) has a unique structure consisting of repeating disaccharide units. Many recent reviews indicated that GAG mediates cell activity, such as proliferation, differentiation and migration, implicating critical roles of GAG play in critical biological processes. Our current experiments showed that CS and HS could mediate ATDC5 chondroprogenitor cell adhesion, proliferation, and chondrogenesis. 6-O-sulfated CS (chondroitin-6-sulfate, C-6-S) promotes chondrogenesis more efficiently than insulin, which was used as an inducer for ATDC5 chondrogenic differentiation. In addition, initial cell density can affect C-6-S-induced chondrogenesis. High inoculation cell density could accelerate chondrogenic differentiation and promote maturation into hypertrophic chondrocyte. In contrast, low density culture could maintain chondrocytic characteristics for a long term culture of 23 days. More interesting, chondrogenesis of ATDC5 cells induced by C-6-S skipped the cellular condensation phenotypes. But it did not affect the expressions of condensation related molecules, Sox9 and N-cadherin. Moreover, the intracellular signal pathways mediating C-6-S induced chondrogenesis was also studies. It indicated that C-6-S induced chondrogenesis via p38 signal pathway. Our studies demonstrated the induction role of C-6-S in chondrogenesis of ATDC5 cells. The obtained information will be helpful on the application of using C-6-S for cartilage repair and for stem cell therapy in cartilage tissue regeneration.
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