Emodin ameliorates cartilage degradation in osteoarthritis by inhibiting NF-κB and Wnt/β-catenin signaling in-vitro and in-vivo.

The overproduction of MMPs (matrix metalloproteinases) and members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family plays an important role in the pathogenesis of osteoarthritis (OA). The potential of selective MMPs or ADAMTS inhibitors as chemopreventive agents for OA has been demonstrated in several studies. In this study, we investigated the protective effects of emodin (1,3,8-trihydroxy-6-methylanthaquinone), isolated from the root of Rheum palmatum L., in the inhibition of MMP and ADAMTS expression in both rat chondrocytes and an animal model of OA. The expression of MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and collagen II mRNA and protein in interleukin-1beta (IL-1β)-induced rat chondrocytes was followed by quantitative real-time PCR and western blot. The activation of the NF-κB and Wnt/β-catenin pathways by IL-1β was assessed by western blot. The in vivo effects of emodin were evaluated by intra-articular injection in rats in an experimental model of OA induced by anterior cruciate ligament transection. Emodin dose-dependently down-regulated the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 at both the mRNA and protein level in IL-1β-stimulated rat chondrocytes. In addition, the IL-1β-induced activation of NF-κB and Wnt signals was attenuated by emodin, as determined by western blotting. The intra-articular injection of emodin in a rat OA model ameliorated OA progression, as determined in morphological and histological analyses in vivo. Taken together, our findings demonstrate that emodin is a promising therapeutic agent for the prevention and treatment of OA.

Ding QH ，Ye CY ，Chen EM ，Zhang W ，Wang XH ... -  《-》

Licochalcone A Inhibits MMPs and ADAMTSs via the NF-κB and Wnt/β-Catenin Signaling Pathways in Rat Chondrocytes.

Osteoarthritis (OA) is a joint disease in which cartilage degradation is the central pathological change. In this study, we investigated the anti-osteoarthritic effects of licochalcone A (Lico A) in rat chondrocytes. Polymerase chain reaction and Western blotting were performed to evaluate the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, ADAMTS-4, collagen II, matrix metalloproteinase (MMP)-13 and MMP-1 at both the gene and protein levels, respectively. In addition, the wnt/β-catenin and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by Western blotting. Lico A downregulated ADAMTS-5, ADAMTS-4,MMP-13 and MMP-1 expression, and diminished the IL-1β-induced inhibition of collagen II. In addition, the activation of β-catenin and phosphorylation of p65 and IKKα/β were suppressed by Lico A. Our results suggest that Lico A inhibits MMPs and ADAMTS partly via the NF-κB and wnt/β-catenin signaling pathways in rat chondrocytes. Thus, Lico A may have therapeutic effects in OA.

Chen WP ，Hu ZN ，Jin LB ，Wu LD ... -  《-》

Polydatin inhibits IL-1β-mediated chondrocyte inflammation and ameliorates cartilage degradation: Involvement of the NF-κB and Wnt/β-catenin pathways.

Hu L ，Luo D ，Zhang H ，He L ... -  《-》

Vildagliptin reduced extracellular matrix degradation in human primary chondrocytes.

In the present study, we investigated the effects of the specific DPP-4 inhibitor vildagliptin on degradation of type II collagen and aggrecan, the main components of the articular extracellular matrix, in primary human chondrocytes. The results of our study reveal that vildagliptin reduced degradation of the articular extracellular matrix (ECM) by downregulating IL-1β-induced expression of matrix metalloproteinases-3 (MMP-3), matrix metalloproteinases-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5). We also found that vildagliptin ameliorated IL-1β-induced activation of the JNK/AP-1 and nuclear factor-κB (NF-κB) pro-inflammatory signaling pathways by downregulating phosphorylation of JNK and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα), activation of c-Fos/c-Jun, and nuclear translocation of p65. Our findings suggest that vildagliptin may serve as a novel treatment for excessive degradation of the articular ECM in osteoarthritis (OA).

Wang Z ，Xu M ，Bai J ，Ge G ，Guo X ，Yu B ，Xiao L ，Geng D ，Hao Y ... -  《-》

Alpha-Mangostin protects rat articular chondrocytes against IL-1β-induced inflammation and slows the progression of osteoarthritis in a rat model.

Osteoarthritis (OA) is a joint disease characterized by inflammation and cartilage degradation. α-Mangostin (α-MG), which can be isolated from the fruit of the tropical evergreen tree Garcinia mangostana-L, is known to have anti-inflammatory properties. The aim of the study was to investigate the use of α-MG in the treatment of OA, using both rat chondrocytes and an OA rat model induced by destabilization of the medial meniscus (DMM). Rat chondrocytes were pretreated with α-MG (0, 1.25, 2.5, and 5.0μg/ml for 24h) prior to stimulation with interleukin-1β (IL-1β) (10ng/ml for 24h). Nitric oxide (NO) production was determined using the Griess method and prostaglandin E2 (PGE2) was assessed using an enzyme-linked immunosorbent assay (ELISA). The expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX-2), matrix metalloproteinase-3, -9, and -13 (MMP-3, MMP-9, and MMP-13), Collagen II, and Aggrecan were detected by both quantitative real-time PCR (qRT-PCR) and a western blot analysis. Nuclear factor-κB (NF-κB) signaling molecules were detected by western blot analysis. Detection of p65 nuclear translocation of NF-κB was examined using immunofluorescence staining. The OA rats received intraperitoneal injections of α-MG (10mg/kg) or saline every other day. Hematoxylin and eosin and Safranin-O-Fast green staining were used to evaluate the severity of cartilage lesions up to 8weeks following surgery. α-MG inhibited the production of NO and PGE2. The elevated expression of INOS, COX-2, MMP-3, MMP-9, and MMP-13, and the degradation of Collagen II and Aggrecan, were reversed by α-MG in IL-1β-stimulated chondrocytes. In addition, IL-1β induced considerable phosphorylation of the NF-kB signaling pathway, which was inhibited by α-MG. Furthermore, the immunofluorescence staining demonstrated that α-MG could suppress IL-1β-induced p65 nuclear translocation. In vivo, cartilage treated with α-MG showed attenuated degeneration and had low Osteoarthritis Research Society International (OARSI) scores compared with the control group. Taken together, these results show that α-MG has potential therapeutic value in the treatment of OA.

Pan T ，Wu D ，Cai N ，Chen R ，Shi X ，Li B ，Pan J ... -  《-》