Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis.

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).

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.

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.

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.

• Authors: Dan Yan, Bingshu He, Jie Guo, Shulan Li, Jun Wang
• Journal: Acta cirurgica brasileira (Acta Cir Bras) Vol. 34 Issue 6 Pg. e201900604 (Aug 19 2019) ISSN: 1678-2674 [Electronic] Brazil
• PMID: 31432995 (Publication Type: Journal Article)

Chemical References

• Interleukin-1beta
• Lipopolysaccharides
• NF-kappa B
• TLR4 protein, human
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Curcumin

Topics

• Animals
• Anterior Cruciate Ligament (pathology, surgery)
• Blotting, Western
• Curcumin (pharmacology)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Injections, Intra-Articular
• Interleukin-1beta (metabolism)
• Lipopolysaccharides
• Male
• NF-kappa B (metabolism)
• Osteoarthritis (chemically induced, metabolism, prevention & control)
• Polymerase Chain Reaction
• Rats
• Toll-Like Receptor 4 (drug effects, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)