Xanthan Gum Ameliorates Osteoarthritis and Mitigates Cartilage Degradation via Regulation of the Wnt3a/β-Catenin Signaling Pathway
Jingyuan Li, Guanying Han, Min Ma, Guohua Wei, Xiaolei Shi, Zhe Guo, Tingting Li, Hai Meng, Yangyang Cao, Xingyuan Liu
The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland)
Med Sci Monit 2019; 25:7488-7498
Available online: 2019-10-06
Osteoarthritis (OA) is a joint disease characterized by articular cartilage degeneration and inflammation. We have previously clarified that a xanthan gum (XG) preparation exerts ameliorating effect on a rabbit OA model by regulating matrix metalloproteinase (MMP)-1 and MMP-3, which are critical proteins in the Wnt3a/ß-catenin pathway. Thus, it is reasonable to predict that the Wnt3a/ß-catenin pathway is involved in the treatment of OA with XG.
MATERIAL AND METHODS: The effect of XG in OA model animals were observed by hematoxylin and eosin staining (HE), Safranin O staining, and Fast Green staining. Articular cartilage degradation on the medial plateau sides was quantified using the modified Pritzker OARSI score. The levels of IL-6, TNF-alpha, and IL-1ß in synovial fluid were determined with ELISA. The protective effect of XG in rat chondrocytes was assessed by CCK8 assay. Moreover, activation of the Wnt3a/ß-catenin pathway and the expression of MMP13, ADAMTS5, aggrecan, and collagen II under the inﬂuence of XG was measured by Western blot and qRT-PCR.
RESULTS: Our results showed that XG reduced the OARSI score and the concentration of inflammatory cytokines in OA after intra-articular injection. XG acted on Wnt3a/ß-catenin in ATDC5 cells in a dose-dependent manner and exhibited a protective effect. XG also decreased the expression of MMP13 and ADAMTS5 and rescued the inhibition of aggrecan and collagen II expression in SNP-stimulated chondrocytes.
CONCLUSIONS: These results indicate that the effects of XG are related to the Wnt3a/ß-catenin pathway and XG suppresses matrix degradation by inhibiting the expression of MMPs and ADAMTS and promotes aggrecan and collagen II content in the ECM, indicating its favorable potential for use in OA therapy.
Keywords: Aggrecans, Cell- and Tissue-Based Therapy, Collagen Type II, Osteoarthritis, Knee, Wnt3A Protein