Boswellia frereana (frankincense) suppresses cytokine‐induced matrix metalloproteinase expression and production of pro‐inflammatory molecules in articular cartilage

Abstract

The aim of this study was to assess the anti-inflammatory efficacy of Boswellia frereana extracts in an in vitro model of cartilage degeneration and determine its potential as a therapy for treating osteoarthritis. Cartilage degradation was induced in vitro by treating explants with 5 ng/ml interleukin1alpha (IL-1alpha) and 10 ng/ml oncostatin M (OSM) over a 28-day period, in the presence or absence of 100 microg/ml B. frereana. Treatment of IL-1alpha/OSM stimulated cartilage explants with B. frereana inhibited the breakdown of the collagenous matrix. B. frereana reduced MMP9 and MMP13 mRNA levels, inhibited MMP9 expression and activation, and significantly reduced the production of nitrite (stable end product of nitric oxide), prostaglandin E2 and cycloxygenase-2. Epi-lupeol was identified as the principal constituent of B. frereana. This is the first report on the novel anti-inflammatory properties of Boswellia frereana in an in vitro model of cartilage degradation. We have demonstrated that B. frereana prevents collagen degradation, and inhibits the production of pro-inflammatory mediators and MMPs. Due to its efficacy we propose that B. frereana should be examined further as a potential therapeutic agent for treating inflammatory symptoms associated with arthritis.

Protein kinase R plays a pivotal role in oncostatin M and interleukin-1 signalling in bovine articular cartilage chondrocytes

“…Our data, showing that OSM+IL-1 potently induced the expression of MMP9 mRNA supports the work of others Blain et al, 2010). Extending these fi ndings, our current study has shown that OSM+IL-1 treatment of articular chondrocytes additionally results in an increase in the activation of proMMP9, a key factor that contributes to joint destruction and infl ammation in the arthritic joint.…”

“…Cells were washed and a goat anti-mouse Alexa 594 conjugated secondary antibody (1:400 dilution; Molecular probes, Invitrogen) applied to the cells for 1 h. Finally, after washing, cells were mounted in VECTASHIELD ® Mounting Medium containing DAPI (1.5 μg/mL) to counterstain DNA (Vector Laboratories, Peterborough, UK). Representative cells from multiple fi elds of view were scanned with a Leica TCS SP2 confocal microscope (Leica, Heidelberg, Germany) using a 63x oil immersion objective lens (x7.5 zoom) as described previously (Blain et al, 2006). To eliminate the possibility of spectral bleed-through between fl uorescent probes, representative regions were scanned using appropriate excitation and emission settings for sequential recordings of DAPI (ex max 358 nm; em max: 461 nm), FITC (excitation max: 494 nm; emission max: 518 nm) and Alexa 594 (excitation max: 594 nm; emission max: 617 nm).…”

“…The cytokine combination of OSM and IL-1 has previously been shown to up-regulate MMP9 expression and activation in nasal cartilage and articular cartilage (Blain et al, 2010). We therefore assessed whether these cytokines could increase MMP9 expression and/or activation in articular chondrocytes via a mechanism involving PKR.…”

“…OSM and IL-1 increase the expression of MMP13 mRNA in articular chondrocytes through a PKR independent mechanism Several studies have shown that treatment of chondrocytes with OSM and IL-1 results in the up-regulation of MMP13 mRNA expression (Koshy et al, 2002;Barksby et al, 2006;Milner et al, 2006;Blain et al, 2010). To determine whether this increase was mediated through the PKR pathway, the expression of MMP13 mRNA was assessed by qPCR following OSM+IL-1 treatment and PKR inhibition (Fig.…”

“…Several studies have shown that OSM signals synergistically with IL-1 in cartilage, inducing collagen (Cawston et al, 1995) and aggrecan (Cawston et al, 1998;Durigova et al, 2011) degradation via up-regulation of MMPs (Blain et al, 2010;Cawston et al, 1998;Hui et al, 2003;Milner et al, 2006) and ADAMTSs (Hui et al, 2005;El Mabrouk et al, 2007;Durigova et al, 2008;Durigova et al, 2011), respectively. In particular, OSM potently induces MMP13 in human and bovine articular cartilage (Fearon et al, 2006;El Mabrouk et al, 2007;Blain et al, 2010) upregulation of which plays a crucial role in the pathology of degenerative joint disease ( (Little et al, 2009) and reviewed in (Takaishi et al, 2008;van den Berg, 2011)). …”