JOURNAL ARTICLE

Chondroprotective effects of glucosamine involving the p38 MAPK and Akt signaling pathways

Yi-Cheng Lin, Yu-Chih Liang, Ming-Thau Sheu, Yu-Chen Lin, Ming-Shium Hsieh, Tzeng-Fu Chen, Chien-Ho Chen
Rheumatology International 2008, 28 (10): 1009-16
18340449
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-1beta. Using chondrosarcoma cells stimulated with IL-1beta, the effects of GLN on the mRNA and protein levels of MMP-3, the activation of JNK, ERK, p38, NF-kappaB, and AP-1, the nuclear translocation of NF-kappaB/Rel family members, and PI3-kinase/Akt activation were studied. GLN inhibited the expression and the synthesis of MMP-3 induced by IL-1beta, and that inhibition was mediated at the level of transcription involving both the NF-kappaB and AP-1 transcription factors. Translocation of NF-kappaB was reduced by GLN as a result of the inhibition of IkappaB degradation. A slightly synergistic effect on the activation of AP-1 induced by IL-1beta 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-1beta treatment, while that for p38 decreased. It was also found that GLN alone, but also synergistically with IL-1beta, was able to activate the Akt pathway. The requirements of NF-kappaB translocation and p38 activity are indispensably involved in the induction of MMP-3 expression in chondrosarcoma cells stimulated by IL-1beta. Inhibition of the p38 pathway in the presence of GLN substantially explains the chondroprotective effect of GLN on chondrocytes that regulate COX-2 expression, PGE(2) 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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
18340449
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"