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Stigmasterol: a phytosterol with potential anti-osteoarthritic properties
Osteoarthritis and Cartilage , 09/18/09

Gabay O et al. – Stigmasterol inhibits several pro-inflammatory and matrix degradation mediators typically involved in OA-induced cartilage degradation, at least in part through the inhibition of the NF-kappa B pathway.

Methods

A model of newborn mouse chondrocytes and human OA chondrocytes in primary culture stimulated with or without IL1beta (10ng/ml), for 18 h was used
Cells were pre-incubated for 48 h with stigmasterol (20 ?g/ml) compared to untreated cells
The presence of stigmasterol in chondrocyte, compared to other phytosterols was studied
The role of stigmasterol on the expression of various genes involved in inflammation (IL-6) and cartilage turn-over (MMP-3,-13, ADAMTS -4, -5, type II collagen, aggrecan) by quantitative RT-PCR was assessed
Additional experiments were carried out to monitor the production of MMP-3 and PGE2 by specific immuno-enzymatic assays
The role of stigmasterol on NF-kappaB activation by western blot, using an anti- I?B? antibody

Results

After 18 h of IL-1? treatment, MMP-3, MMP-13, ADAMTS-4, but not ADAMTS-5 RNA expression were elevated, as well as MMP-3 and PGE2 protein levels in mouse and human chondrocytes
Type II collagen and aggrecan mRNA levels were significatively reduced
Pre-incubation of stigmasterol to IL1-beta-treated cells significantly decreased these effects described above (significant reduction of MMP-3 mRNA in human and mouse, MMP-3 protein in mouse, MMP-13 mRNA in mouse and human, ADAMTS-4 mRNA in human, PGE2 protein in human and mouse) Finally, stigmasterol was capable of counteracting the IL-1beta-induced NF-kappa B pathway

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