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Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis.
- Source :
-
Acta cirurgica brasileira [Acta Cir Bras] 2019 Aug 19; Vol. 34 (6), pp. e201900604. Date of Electronic Publication: 2019 Aug 19. - Publication Year :
- 2019
-
Abstract
- Purpose: In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT).<br />Methods: The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1 and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively.<br />Results: Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees.<br />Conclusion: The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.
- Subjects :
- Animals
Anterior Cruciate Ligament pathology
Blotting, Western
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Injections, Intra-Articular
Interleukin-1beta metabolism
Lipopolysaccharides
Male
NF-kappa B metabolism
Osteoarthritis chemically induced
Osteoarthritis metabolism
Polymerase Chain Reaction
Rats
Toll-Like Receptor 4 drug effects
Tumor Necrosis Factor-alpha metabolism
Anterior Cruciate Ligament surgery
Curcumin pharmacology
Osteoarthritis prevention & control
Toll-Like Receptor 4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1678-2674
- Volume :
- 34
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Acta cirurgica brasileira
- Publication Type :
- Academic Journal
- Accession number :
- 31432995
- Full Text :
- https://doi.org/10.1590/s0102-865020190060000004