RRC ID 54738
Author Pirozzi C, Francisco V, Guida FD, Gómez R, Lago F, Pino J, Meli R, Gualillo O.
Title Butyrate Modulates Inflammation in Chondrocytes via GPR43 Receptor.
Journal Cell Physiol Biochem
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.
Volume 51(1)
Pages 228-243
Published 2018-11-16
DOI 10.1159/000495203
PII 000495203
PMID 30448827
MeSH Adipokines / metabolism Animals Annexin A1 / metabolism Butyric Acid / pharmacology* Cell Adhesion Molecules / metabolism Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism Collagen Type II / genetics Collagen Type II / metabolism Cyclooxygenase 2 / metabolism Inflammation Mediators / metabolism Interleukin-1beta / pharmacology Matrix Metalloproteinase 13 / genetics Matrix Metalloproteinase 13 / metabolism Mice NF-kappa B / metabolism Nitric Oxide Synthase Type II / genetics Nitric Oxide Synthase Type II / metabolism RNA Interference RNA, Small Interfering / metabolism Receptors, G-Protein-Coupled / antagonists & inhibitors Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism* Signal Transduction / drug effects*
IF 5.5
Times Cited 8
Human and Animal Cells ATDC5(RCB0565)