Vasoactive intestinal peptide alleviates osteoarthritis effectively via inhibiting NF-κB signaling pathway

Abstract

BackgroundTo investigate the treatment effect of vasoactive intestinal peptide (VIP) on osteoarthritis (OA) and the relative mechanism.MethodThe OA model on the SD rat knee was established using the modified Hulth method, and the recombinant pcDNA3.1+/VIP plasmid was constructed. One month after the plasmids VIP were injected intra-articularly into the right knee joint of OA and sham-operated rats, the pathological changes of the OA knee joint were observed by Hematoxylin-eosin (HE) and Safranin O/fast green staining. The levels of VIP and serum inflammatory cytokines (TNF-α, IL-2 and IL-4) were measured by ELISA kits. Meanwhile, synoviocytes isolated from OA rat and sham-operated rat were cultured in vitro, and transfected with the VIP plasmid. The proliferation of synoviocytes was determined using BrdU kits. The protein expressions of TNF-α, IL-2, CollagenII, osteoprotegerin (OPG), matrix-degrading enzymes (MMP-13, ADAMTS-5), and the related protein of NF-κB signaling pathway (phosphorylated p65, phosphorylated IκBα) were evaluated by western blot.ResultsThe VIP plasmid could effectively improve the pathological state of the OA rats knee joint, significantly decrease the levels of serum TNF-α and IL-2, and clearly increase the levels of VIP and serum IL-4. At the same time, after the OA synoviocytes were treated with the VIP plasmid, the proliferation ability of OA synoviocytes was reduced, the protein expressions of Collagen II and OPG were remarkably up-regulated, and the protein expressions of TNF-α, IL-2, MMP-13 and ADAMTS-5 were significantly down-regulated. In addition, the p-p65 expression decreased and p-IκBα expression increased.ConclusionOsteoarthritis was effectively treated by VIP via inhibiting the NF-κB signaling pathway.

Identification of CSPG4 as a promising target for translational combinatorial approaches in osteosarcoma

“…Indeed, CSC are thought to be the main drivers of OSA-related death, being responsible for tumor chemoresistance, finally resulting in recurrence and metastasis. 40 Starting from this assumption, we generated MG-63 (Supplemental Figure S4(a)) and Penny (Supplemental Figure S4(b)) derived osteospheres, following the protocol described by Conti and coworkers. 33 Interestingly human (Supplemental Figure S4(c)) and canine (Supplemental Figure S4(d)) osteosphere-derived cells expressed high levels of CSPG4, making it an even more interesting antigen for the immune-targeting of both differentiated cancer cells and CSC in OSA.…”

Integration of Gene Expression Profile Data to Screen and Verify Hub Genes Involved in Osteoarthritis

“…Tumor necrosis factor (TNF) is a critical cytokine, which can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity [ 29 ]. TNF- α mediated activation of NF- κ B signaling pathway is known to play an important role in the pathogenesis of OA [ 30 ], and OA was effectively treated by VIP via inhibiting the NF- κ B signaling pathway [ 31 ]. Cytokines which are produced in joint tissues regulate a broad range of inflammatory processes [ 32 ]; the occurrence and development of OA are driven by various mediators, of which the key role is attributed to the interactions within the cytokine-cytokine network.…”

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

“…VIP reduces the serum levels of TNF-α and IL-2 and increases serum IL-4 in a rat model of knee OA. In this model, VIP also inhibits proliferation of OA-SF and decreases the production of TNF-α, IL-2, MMP-13, and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs-5), at the same time that it induces the expression of type II collagen and osteoprotegerin, by inhibition of NFκB signaling [232,233]. In addition, VIP modulates the corticotropin-releasing factor family of neuropeptides, also increasing the expression of the potential anti-inflammatory mediators UCN-2 and -3, as well as CRFR2 in OA-SF.…”