Vitamin D3 protects articular cartilage by inhibiting the Wnt/[beta]-catenin signaling pathway

Low expression levels of 25-hydroxyvitamin D (vitamin D3) in the blood have been reported to be associated with the progression of osteoarthritis; however, the mechanisms by which this occurs remain unclear. The present study aimed to determine the effects of vitamin D3 on chondrocytes. MTT assays were used to determine whether vitamin D3 affects chondrocytes viability. Primary chondrocytes were treated with control culture medium, vitamin D3, tumor necrosis factor (TNF)-[alpha], TNF-[alpha] + PNU-74654 [Wingless-related integration site (Wnt)/[beta]-catenin signaling pathway inhibitor] or TNF-[alpha] + vitamin D3. Reverse transcription-quantitative PCR and western blotting were utilized to measure the gene and protein expression of collagen II, aggrecan, matrix metalloproteinase (MMP)-3 and MMP-13, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, Wnt-3a and nuclear [beta]-catenin. The results demonstrated that TNF-[alpha] reduced the expression levels of aggrecan and collagen II, and increased the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5. Furthermore, vitamin D3 and PNU-74654 were observed to partially attenuate the effects induced by TNF-[alpha]. Moreover, similar findings were reported following co-treatment with vitamin D3 and TNF-[alpha]. Western blotting data revealed that TNF-[alpha] increased Wnt-3a and [beta]-catenin protein levels in chondrocytes, while Vitamin D3 and PNU-74654 decreased the expression levels of Wnt-3a and nuclear [beta]-catenin. In conclusion, the findings of the present study provided evidence to suggest that vitamin D3 may prevent articular cartilage degeneration and osteoarthritic disease progression by inhibiting the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 through suppressing the Wnt/[beta]-catenin signaling pathway. These results suggested that vitamin D3 may be of therapeutic value for the prevention and treatment of osteoarthritis. Key words: vitamin D3, Wnt/[beta]-catenin, osteoarthritis, cartilage, chondrocyte