Luteolin Inhibits the Activity, Secretion and Gene Expression of MMP-3 in Cultured Articular Chondrocytes and Production of MMP-3 in the Rat Knee

Abstract

We investigated whether luteolin affects the gene expression, secretion and activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as production of MMP-3 in the rat knee to evaluate the potential chondro-protective effects of luteolin. Rabbit articular chondrocytes were cultured in a monolayer and IL-1β-induced gene expression levels of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen were measured by reverse transcription - polymerase chain reaction (RT-PCR). Effects of luteolin on interleukin-1β (IL-1β)-induced secretion and enzyme activity of MMP-3 in rabbit articular chondrocytes were investigated by western blot analysis and casein zymography, respectively. The effect of luteolin on MMP-3 protein production was also examined in vivo. The results were as follows: (1) luteolin inhibited the gene expression levels of MMP-3, MMP-1, MMP-13, ADAMTS-4 and ADAMTS-5. However, it increased the gene expression level of collagen in rabbit articular chondrocytes; (2) luteolin inhibited the secretion and activity of MMP-3; (3) luteolin inhibited in vivo production of MMP-3 protein. These results suggest that luteolin can regulate the gene expression, secretion and activity of MMP-3, by directly acting on articular chondrocytes.

Nobiletin Inhibits Expression of Inflammatory Mediators and Regulates JNK/ERK/p38 MAPK and PI3K/Akt Pathways in Human Osteoarthritic Chondrocytes

“…Previous studies have shown increased expression of MMPs, COX-2, and iNOS following stimulation of chondrocytes by IL-1β [25]. Thus, the results indicate that nobiletin exerts antiinflammatory effects via attenuation of NF-κB activity.…”

Mechanism of Salviae Miltiorrhizae Radix et Rhizoma in the treatment of knee osteoarthritis based on network pharmacology

“…Two fat-soluble terpenoids of tanshinone IIA from SMRR were identi ed. Tanshinone IIA protects ATDC5 cells from lipopolysaccharide-induced in ammatory injury by downregulating microRNA-203a and inhibiting the JAK/STAT and JNK pathways [32]. Tanshinone IIA can also inhibit the proliferation of chondrocytes, and the degree of inhibition is positively correlated with the concentration of tanshinone IIA.…”

“…In addition, experimental studies in rats showed that luteolin could improve the effect of superoxide dismutase (SOD) and catalase induced by selenite, enhance the activity of glutathione peroxidase and glutathione reductase, and then, enhance the activity of the antioxidant enzyme system in organisms [31]. It has also been reported that luteolin can regulate the expression, secretion and activity of MMP-3 by directly acting on articular chondrocytes [32].…”

Coenzyme Q10 Prevents the Interleukin‐1 Beta Induced Inflammatory Response via Inhibition of MAPK Signaling Pathways in Rat Articular Chondrocytes

“…To control the progression of the OA, pharmacological and dietary methods have been used [Kaneva et al, ; Xu et al, ]. Previous studies have showed that natural products might be useful for the treatment of OA and rheumatoid arthritis [Kang et al, ; Liu et al, ; Moon et al, ]. CoQ10, an endogenous antioxidant, can suppress the IL‐1β‐induced inflammatory response in some diseases [Fuller et al, ; Schmelzer et al, ].…”