The effect of celecoxib in traumatic heterotopic ossification around temporomandibular joint in mice
The effect of celecoxib in traumatic heterotopic ossification around temporomandibular joint in mice
复制标题
塞来昔布对小鼠颞下颌关节周围创伤性异位骨化的影响
DOI：
10.1016/j.joca.2020.01.014
复制
发表时间：
2020-04-01
影响因子：
7
通讯作者：
Shen, G.
中科院分区：
文献类型：
--
作者：
Ouyang, N.;Zhao, Y.;Shen, G.
目的：本研究探讨炎症在创伤性颞下颌关节周围异位骨化（thom - tmj）中的作用，以及塞来昔布在体内和体外对thom - tmj的预防和治疗作用。设计：采用手术诱导的THO-TMJ小鼠模型和ATDC-5或MC3T3-E1与RAW-264.7细胞共培养模型进行体内和体外研究。结果：THO-TMJ模型损伤48 h后，CD3、CD68、CD20、IL-10、IL-6、tnf - α等一系列炎症因子被激活。局部创伤引发全身炎症反应，以及T细胞和巨噬细胞介导的TMJ周围局部炎症反应。COX-2表达明显升高。研究结果还表明，局部注射塞来昔布可有效缓解创伤早期TMJ周围的炎症反应，体内可抑制THO-TMJ的形成。同时，塞来昔布在体外炎症条件下可抑制ATDC-5的软骨分化和MC3T3-E1的成骨分化。此外，塞来昔布可抑制THO-TMJ发病初期损伤髁软骨中Bmpr1b的表达，提示残留髁软骨表达Bmpr1b可能与THO-TMJ发病机制有关。结论：炎症在THO-TMJ的发病机制中起着至关重要的作用，抗炎可能是抑制THO-TMJ的可能选择，为THO-TMJ的发病机制、药物治疗和分子干预提供了科学线索。(C) 2020由爱思唯尔有限公司代表国际骨关节炎研究学会出版。
Objective: In this study, the role of inflammation in traumatic heterotopic ossification around temporomandibular joint (THO-TMJ), as well as the preventive and treatment effect of celecoxib in THO-TMJ both in vivo and in vitro were explored.Design: A surgically-induced THO-TMJ mouse model and a co-culture model of ATDC-5 or MC3T3-E1 and RAW-264.7 cells were used in this study for in vivo and in vitro research.Results: A series of inflammatory factors, such as CD3, CD68, CD20, IL-10, IL-6 and TNF-alpha, were activated 48 h after trauma in a THO-TMJ model. Local trauma initiated systemic inflammatory responses as well as T cell- and macrophage-mediated local inflammatory responses around TMJ. In addition, expression of COX-2 was significantly elevated. The findings also showed that local injection of celecoxib could effectively alleviate the inflammatory response around TMJ at the early stage of trauma and inhibit the formation of THO-TMJ in vivo. Meanwhile, celecoxib could inhibit chondrogenic differentiation of ATDC-5 and osteogenic differentiation of MC3T3-E1 under inflammatory condition in vitro. Furthermore, celecoxib could inhibit the expression of Bmpr1b in the injured condylar cartilage at the initiation stage of THO-TMJ, which implied that Bmpr1b expressed by the residual condylar cartilage might be related to the pathogenesis of THO-TMJ.Conclusions: Inflammation played a crucial role in the pathogenesis of THO-TMJ, and anti-inflammation might be a possible choice to inhibit THO-TMJ, which provided scientific clues for the mechanisms, pharmacotherapy and molecular intervention of THO-TMJ. (C) 2020 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.