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

Abstract The purpose of the present study was to
elucidate the possible signal transduction pathway involved
in the underlying mechanism of glucosamine (GLN)’s
inXuence on the gene expression of matrix metalloproteinases
(MMPs) in chondrocytes stimulated with IL-1. Using
chondrosarcoma cells stimulated with IL-1, the eVects of
GLN on the mRNA and protein levels of MMP-3, the
activation of JNK, ERK, p38, NF-B, and AP-1, the
nuclear translocation of NF-B/Rel family members, and
PI3-kinase/Akt activation were studied. GLN inhibited the
expression and the synthesis of MMP-3 induced by IL-1,
and that inhibition was mediated at the level of transcription
involving both the NF-B and AP-1 transcription
factors. Translocation of NF-B was reduced by GLN as a
result of the inhibition of IB degradation. A slightly synergistic
eVect on the activation of AP-1 induced by IL-1 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-1 treatment, while that for
p38 decreased. It was also found that GLN alone, but also
synergistically with IL-1, was able to activate the Akt
pathway. The requirements of NF-B translocation and p38
activity are indispensably involved in the induction of
MMP-3 expression in chondrosarcoma cells stimulated by
IL-1. Inhibition of the p38 pathway in the presence of
GLN substantially explains the chondroprotective eVect of
GLN on chondrocytes that regulate COX-2 expression,
PGE2 synthesis, and NO expression and synthesis. The
chondroprotective eVect of GLN through the decrease in
MMP-3 production and stimulation of proteoglycan synthesis
may follow another potential signaling pathway of Akt.