cular chondrocytes, Tivantinib while the peak of phosphorylation last from 15 min to 60 min. Then, the phosphorylation status of both SAP JNK and p38 MAPK started to fade after 60 min. However, the activation of phosphorylation of SAP JNK and p38 MAPK by IL 1B were obviously reduced by the pretreated SP600125 and SB203580, respectively. Further, SB203580 promoted GAG synthesis and UGDH mRNA e pression but not affected the trans regulators, while SP600125 affected none of these process. However, IL 1B inhibited GAG synthesis and gene e pression of UGDH, Sp1 and Sp3, but stimulated c Kro gene e pression, while both SB203580 and SP600125 attenuated the effect of IL 1B on these process, which indicated that both p38 MAPK pathway and SAP JNK pathway were involved in the IL 1B modulated UGDH gene e pression.
Discussions Its well known that the content of PGs is most abundant in the mid zone of articular cartilage, rather than the superficial or deep zones, for chondrocytes in the mid zone highly synthesis both PGs and collagens, while chondrocytes in the superficial and deep zones mainly synthesize collagens instead of PGs. Meanwhile, chondrocytes in the mid zone but not the superficial or deep zones of articular cartilage present a high UGDH activity, which indicated a possible correlation between UGDH enzyme activity and PGs synthesis in articular chondrocytes. Moreover, evidences also indicated that UGDH determines hyaluronan synthesis in prostate cancer cells, which thus promotes the metastasis progression of the cancer cells, while the stimulated UGDH e pression by TGF B could promote hyaluronan production in chick articular surface cells.
In the present study, suppressing UGDH gene e pression led to an obvious decrease in PGs synthesis in human articular chondrocytes. Taken together, these findings suggest that UGDH plays a critical role in the PGs synthesis of articular chondrocytes, although the Batimastat intracellular synthesis of UDP glucuronic acid was not measured in the present study. As PGs are the key components in the cartilage matri , which maintain the fluid and electrolyte balance, and provide the living space of chondrocytes and the elasticity of the cartilage, we speculate that UGDH might further be an essential player in maintaining cartilage homeostasis.
As a typical degenerative disease of articular cartilage, OA starts with the disturbance of cartilage homeostasis, which leads to the subsequent loss of cartilage matri and disorganization of articular cartilage. However, no correlation between selleck bio the PGs loss and UGDH in OA has been reported, e cept Zemel et al. who indicated that no significant increase in UGDH activity was observed between human normal and OA chondrocytes, and that the lack of significantly enhanced UGDH activity could contribute to continuous GAG loss during OA progress. In the present study, we found, for the first time, that protein level of UGDH is obviously lower in DC than that of MNC from the same OA patient, while chondrocyte