Open AccessButyrate Modulates Inflammation in Chondrocytes via GPR43 Receptor
Author(s) -
Claudio Pirozzi,
Vera Francisco,
Francesca Guida,
Rodolfo Gómez,
Francisca Lago,
Jesús Pino,
Rosaria Meli,
Oreste Gualillo
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000495203
Subject(s) - inflammation , sodium butyrate , chemokine , chemotaxis , chemistry , chondrocyte , adipokine , cancer research , immunology , microbiology and biotechnology , cartilage , receptor , medicine , biology , leptin , biochemistry , gene , obesity , anatomy
Background/Aims: Osteoarthritis (OA) is a joint degenerative biomechanical disorder involving immunity, metabolic alterations, inflammation, and cartilage degradation, where chondrocytes play a pivotal role. OA has not effective pharmacological treatments and new therapeutic targets are needed. Adipokines contribute to the low-grade systemic inflammation in OA. Here, we explored novel molecular mechanisms of sodium butyrate (BuNa) in modulating inflammation and chemotaxis in chondrocytes, demonstrating the direct involvement of its G protein-coupled receptor (GPR)-43. Methods: ATDC5 murine chondrocytes were stimulated with interleukin (IL)-1β, in the presence or not of BuNa, for 24 h. RT-PCR and Western blot analysis was performed to evaluate the expression of inflammatory mediators and structural proteins. Results: Butyrate reduced the expression of canonic pro-inflammatory mediators (Nos2, COX-2, IL-6), pro-inflammatory adipokines (lipocalin-2 and nesfatin-1) and adhesion molecule (VCAM-1 and ICAM-1) in IL-1β-stimulated chondrocytes, inhibiting several inflammatory signalling pathways (NFκB, MAPKinase, AMPK-α, PI3K/Akt). Butyrate also reduced metalloproteinase production and limited the loss of type II collagen in IL-1β-inflamed chondrocytes. The chemoattractant effect of butyrate, after different inflammatory challenges, was revealed by increased annexin (AnxA)1 levels and chemokines expression. The chemoattractant and anti-inflammatory activities of butyrate were completely blunted by GPR43 silencing using RNA interference. Conclusion: Taken together, our data suggest the potential application of sodium butyrate as a novel candidate in a multi-target approach for the treatment of chondrocyte inflammation and cartilage degenerative process.