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.
Butyrate modulates inflammation in chondrocytes via GPR43 receptor / Pirozzi, Claudio; Francisco, Vera; Guida, Francesca Di; Gómez, Rodolfo; Lago, Francisca; Pino, Jesus; Meli, Rosaria; Gualillo, Oreste. - In: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY. - ISSN 1015-8987. - 51:1(2018), pp. 228-243. [10.1159/000495203]
Butyrate modulates inflammation in chondrocytes via GPR43 receptor
Pirozzi, Claudio
Primo
;Meli, RosariaMembro del Collaboration Group
;Gualillo, Oreste
2018
Abstract
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.File | Dimensione | Formato | |
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