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  3. Medizin - Open Access LMU - Teil 17/22 Podcast
  4. IGF-1 and PDGF-bb suppress IL-1β-induced cartilage degradation through down-regulation of NF-κB signaling: involvement of Src/PI-3K/AKT pathway.
Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a
key role in the pathogenesis of osteoarthritis (OA). Growth factors
(GFs) capable of antagonizing the catabolic actions of cytokines
may have therapeutic potential in the treatment of OA. Herein, we
investigated the potential synergistic effects of insulin-like
growth factor (IGF-1) and platelet-derived growth factor (PDGF-bb)
on different mechanisms participating in IL-1β-induced activation
of nuclear transcription factor-κB (NF-κB) and apoptosis in
chondrocytes. Primary chondrocytes were treated with IL-1β to
induce dedifferentiation and co-treated with either IGF-1 or/and
PDGF-bb and evaluated by immunoblotting and electron microscopy.
Pretreatment of chondrocytes with IGF-1 or/and PDGF-bb suppressed
IL-1β-induced NF-κB activation via inhibition of IκB-α kinase.
Inhibition of IκB-α kinase by GFs led to the suppression of IκB-α
phosphorylation and degradation, p65 nuclear translocation and
NF-κB-regulated gene products involved in inflammation and
cartilage degradation (COX-2, MMPs) and apoptosis (caspase-3). GFs
or BMS-345541 (specific inhibitor of the IKK) reversed the
IL-1β-induced down-regulation of collagen type II, cartilage
specific proteoglycans, β1-integrin, Shc, activated MAPKinase,
Sox-9 and up-regulation of active caspase-3. Furthermore, the
inhibitory effects of IGF-1 or/and PDGF-bb on IL-1β-induced NF-κB
activation were sensitive to inhibitors of Src (PP1), PI-3K
(wortmannin) and Akt (SH-5), suggesting that the pathway consisting
of non-receptor tyrosine kinase (Src), phosphatidylinositol
3-kinase and protein kinase B must be involved in IL-1β signaling.
The results presented suggest that IGF-1 and PDGF-bb are potent
inhibitors of IL-1β-mediated activation of NF-κB and apoptosis in
chondrocytes, may be mediated in part through suppression of
Src/PI-3K/AKT pathway, which may contribute to their
anti-inflammatory effects.

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„IGF-1 and PDGF-bb suppress IL-1β-induced cartilage degradation through down-regulation of NF-κB signaling: involvement of Src/PI-3K/AKT pathway.“

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