Inhibition of Nf-ҝb prevents trauma-induced heterotopic ossification in rat model

Abstract

Background. To find a better prophylactic regimen, the pathogenesis of acquired heterotopic ossification (AHO) must be more understood. To date, AHO formation is largely thought to be related to inflammation, which is activated by trauma, resulting in AHO by up-regulation of pro-osteogenic genes. Methods. Brain-traumatic/burn/tenotomy model is firstly used in experiment. At first, 44 rats were randomly divided into two groups: E group and C group. Two rats in every group were euthanized during second, third, fourth, sixth, eighth, tenth weeks for collecting tendon. The remaining rats survived until tenth week for X-Ray radiation examination to confirm the size of AHO.Then, 124 rats were randomly divided into four group: P group, L group, M group, H group. The three rats of every group were euthanized during every week of the first seven weeks for collecting tendon to detect P65 protein. The remaining rats survived until tenth week for X-Ray examination to confirm the size of AHO. Results. The success rate of Brain-traumatic/Burn/Tenotomy model is 100%. Difference of P65 expression in E group and in C group are statistically significant,and that in E group is higher.Pharmacologic inhibition of Nf-ҝb signaling pathway limits AHO formation, and that The bone formation content of M group is decreased. Conclusion. Brain-traumatic/Burn/Tenotomy model is highly reliable.Results indicate that the Nf-ҝb /p65 signaling response occurs in the forming process of AHO. PDTC limits formation of AHO. The most effective concentration is 6mg/ml for local injection.

Quercetin Attenuates Trauma-Induced Heterotopic Ossification by Tuning Immune Cell Infiltration and Related Inflammatory Insult

“…However, after SRT1720 HCI treatment, acetylated NFκB p65 expression was largely weakened, paralleled by the reduced macrophage and mast cell presence and consistent with the assumption that the immunomodulatory effects of SIRT1 may be due to altered NFκB signaling. In accordance with this finding, prolonged NFκB pathway activation was found in monocytes and macrophages from FOP patients ( 16 ), and pharmacological inhibition of canonical NFκB signaling also abrogated HO in a rat brain-traumatic/burn/tenotomy model ( 54 ). Altogether, we showed that impaired SIRT1/NFκB signaling was responsible for aberrant immunity during HO development.…”

Palovarotene inhibits the NF‐κB signalling pathway to prevent heterotopic ossification

“…The results demonstrated that palovarotene reversed osteogenic differentiation of BMSCs under the influence of IL‐1β. According to our previous findings, the NF‐κB signalling pathway may be involved in the osteogenic differentiation of BMSCs 16 . To verify this hypothesis; we performed western blotting and immunofluorescence assays.…”

“…According to our previous findings, the NF-κB signalling pathway may be involved in the osteogenic differentiation of BMSCs. 16 To verify this hypothesis; we performed western blotting and immunofluorescence assays. We focused on the core molecule of the NF-κB signalling pathway, p65 and the immunofluorescence results The animals were divided into six groups as follows: control 1 and 2, model 1 and 2, and palovarotene and PDTC.…”