Curcumin Inhibits Proliferation of Synovial Cells by Downregulating Expression of Matrix Metalloproteinase‐3 in Osteoarthritis

Abstract

Objective To investigate the association between curcumin and the differentially expressed genes (DEG) in synovial tissues of osteoarthritis. Methods Microarray analysis was used to screen for the DEG in osteoarthritis synovial cells. Curcumin‐related genes were identified through the drug–gene interaction network STITCH ( http://stitch.embl.de/cgi/input.pl ). Expression levels of fibronectin 1 (FN1) and collagen III protein were measured by western blot. MTT assay was used to examine the effects of different concentrations of curcumin on cell viability. Western blot and quantitative real‐time polymerase chain reaction were used to validate the different expression levels of matrix metalloproteinase‐3 (MMP3). Clone formation assay, flow cytometry, and the TUNEL method were conducted for detecting the cell proliferation and apoptosis rate. Results In the two chips of GSE1919 and GSE55235, the average expression of MMP3 in the osteoarthritis group was 63.7% and 12.9% higher than that of the healthy control, respectively. The results of western blot also showed that the average expression of MMP3 in 30 osteoarthritis patients was 132% higher than that of the healthy group, which confirmed that MMP3 was highly expressed in osteoarthritis group. The results of MTT showed that at 72 h, the cell viability of 40 μmol/L curcumin was the lowest and 79.6% lower than for the 0 μmol/L group, so the final curcumin concentration of 40 μmol/L was selected for subsequent experiments. Western blot results further showed that the expression of MMP3 was 44% lower in the untreated groups compared with the curcumin group, and the expressions of FN1 and collagen III were increased by 112% and 84%, respectively, which indicated that curcumin inhibited MMP3 expression and decreased osteoarthritis synovial cell activity. Cloning formation experiments showed that cell numbers increased by 75% and 20.5% in untreated and curcumin groups, and compared with the untreated group, the cells in the curcumin group decreased by 30.8%. Flow cytometry showed that the apoptotic rate in the curcumin group increased by 85.1% compared with the untreated group, but for a single group, MMP3 decreased the apoptotic rate by 53.9% and 46.7%, respectively. Conclusions MMP3 was highly expressed in osteoarthritis synovial cells. Curcumin could reduce cell viability, inhibit cell proliferation, increase cell apoptosis, and eventually alleviate inflammation of osteoarthritis by inhibiting the expression of MMP3.

New Paradigms to Assess Consequences of Long-Term, Low-Dose Curcumin Exposure in Lung Cancer Cells

“…Such high doses are unlikely to be attained clinically, making it difficult to interpret and translate mechanistic relevance to prevention strategies that are typified by sub-micromolar systemic curcuminoid availability. High-dose curcumin has been shown specifically to inhibit the EMT-associated proteins snail [20], lumican [21], CCL2 [22], cathepsin B [23], carbonic anhydrase [24], and matrix metalloproteinase-3 [25], all of which we also show here to have been significantly downregulated following long-term, low-dose curcumin. Some of these proteins exhibited prolonged downregulation even following a three-month withdrawal period from curcumin treatment.…”

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

“…36 As reported by Zeng et al, curcumin, a component extracted from Curcuma longa, alleviated inflammation of OA by down-regulating the level of MMP3, inhibiting cell proliferation and inducing cell apoptosis. 37 At this point, we elucidated the role of Sal in OA in vivo. The results demonstrated Sal has a significant therapeutic effect on OA rats.…”

Increased elastic modulus of the synovial membrane in a rat ACLT model of osteoarthritis revealed by atomic force microscopy

“…MMP-3 is a member of the MMP family and has been shown to be involved in a variety of inflammatory and oncological conditions. It was reported that MMP-3 is highly expressed in the synovial cells of osteoarthritis and can promote the proliferation of synovial cells and inhibit apoptosis (38). In addition, Chen et al (39) found that reduction of MMP-3 mRNA and protein expression can protect the cartilage and treat osteoarthritis.…”