Abstract
The purpose of the present study was to elucidate the possible signal transduction pathway involved in the underlying mechanism of glucosamine (GLN)’s influence on the gene expression of matrix metalloproteinases (MMPs) in chondrocytes stimulated with IL-1β. Using chondrosarcoma cells stimulated with IL-1β, the effects of GLN on the mRNA and protein levels of MMP-3, the activation of JNK, ERK, p38, NF-κB, and AP-1, the nuclear translocation of NF-κB/Rel family members, and PI3-kinase/Akt activation were studied. GLN inhibited the expression and the synthesis of MMP-3 induced by IL-1β, and that inhibition was mediated at the level of transcription involving both the NF-κB and AP-1 transcription factors. Translocation of NF-κB was reduced by GLN as a result of the inhibition of IκB degradation. A slightly synergistic effect on the activation of AP-1 induced by IL-1β was shown in the presence of GLN. Among MAPK pathways involved in the transcriptional regulation of AP-1, phosphorylation of JNK and ERK was found to increase with the presence of GLN under IL-1β treatment, while that for p38 decreased. It was also found that GLN alone, but also synergistically with IL-1β, was able to activate the Akt pathway. The requirements of NF-κB translocation and p38 activity are indispensably involved in the induction of MMP-3 expression in chondrosarcoma cells stimulated by IL-1β. Inhibition of the p38 pathway in the presence of GLN substantially explains the chondroprotective effect of GLN on chondrocytes that regulate COX-2 expression, PGE2 synthesis, and NO expression and synthesis. The chondroprotective effect of GLN through the decrease in MMP-3 production and stimulation of proteoglycan synthesis may follow another potential signaling pathway of Akt.
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Financial support by Mackay Memorial Hospital (94MMH-TMU-14) is highly appreciated.
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Yi-Cheng Lin and Yu-Chih Liang equally contributed to this work.
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Lin, YC., Liang, YC., Sheu, MT. et al. Chondroprotective effects of glucosamine involving the p38 MAPK and Akt signaling pathways. Rheumatol Int 28, 1009–1016 (2008). https://doi.org/10.1007/s00296-008-0561-4
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DOI: https://doi.org/10.1007/s00296-008-0561-4