Cortistatin binds to TNF-α receptors and protects against osteoarthritis

Abstract

Background Osteoarthritis (OA) is a common degenerative disease, and tumor necrosis factor (TNF-α) is known to play a critical role in OA. Cortistatin (CST) is a neuropeptide discovered over 20 years ago, which plays a vital role in inflammatory reactions. However, it is unknown whether CST is involved in cartilage degeneration and OA development. Methods The interaction between CST and TNF-α receptors was investigated through Coimmunoprecipitation and Biotin-based solid-phase binding assay. Western blot, Real-time PCR, ELISA, immunofluorescence staining, nitrite production assay and DMMB assay of GAG were performed for the primary chondrocyte experiments. Surgically induced and spontaneous OA models were established and western blot, flow cytometry, Real-time PCR, ELISA, immunohistochemistry and fluorescence in vivo imaging were performed for in vivo experiments. Findings CST competitively bound to TNFR1 as well as TNFR2. CST suppressed proinflammatory function of TNF-α. Both spontaneous and surgically induced OA models indicated that deficiency of CST led to an accelerated OA-like phenotype, while exogenous CST attenuated OA development in vivo. Additionally, TNFR1- and TNFR2-knockout mice were used for analysis and indicated that TNFRs might be involved in the protective role of CST in OA. CST inhibited activation of the NF-κB signaling pathway in OA. Interpretation This study provides new insight into the pathogenesis and therapeutic strategy of cartilage degenerative diseases, including OA. Fund The , the , .

Potential efficacy of gut microbiome dysbiosis on alleviation the progress of osteoarthritis in mice

“…In OA pathogenesis particularly in synovial in ammation, activated chondrocytes and synovial broblasts (TNF-α and IL-6) have been identi ed as vital players [46]. Zhao et.al found that both spontaneous and surgically induced OA models indicated that TNF-α led to an accelerated OA-like phenotype [47]. TNF-α control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies [48].…”

Systematic elucidation of the molecular mechanism of scutellarin against osteoarthritis based on network pharmacology

“…So, our data were partly in accordance with previous data. In addition, we also identi ed new signaling pathways including TNF signaling pathway, NOD-like receptor signaling pathway and HIF-1 signaling pathway, which were all the core signaling pathway in the pathogenesis of OA [31][32][33][34][35][36], thus may be involved in the inhibitive effect of Scutellarin on OA. Our data will be the supplement for the present studies on the molecular mechanisms of Scutellarin against OA.…”

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

“…In addition, TNF-α is an important mediator of cartilage matrix degradation and can play an important role in the process of synovitis and cartilage tissue degradation. TNF-α participates in in ammation by binding to the receptors TNFR1 and TNFR2 [82]. It combines with TNFRI to induce COX-and stimulate synovial cells to produce PGE and chondrocytes to produce peroxidation, leading to the destruction of bone and cartilage [82].…”

“…TNF-α participates in in ammation by binding to the receptors TNFR1 and TNFR2 [82]. It combines with TNFRI to induce COX-and stimulate synovial cells to produce PGE and chondrocytes to produce peroxidation, leading to the destruction of bone and cartilage [82]. Furthermore, TNF-α activates the NF-κB signaling pathway by binding to receptors TNFR1 and TNFR2, leading to IκBα phosphorylation.…”