Increased chemokine RANTES in synovial fluid and its role in early-stage degenerative temporomandibular joint disease
Increased chemokine RANTES in synovial fluid and its role in early-stage degenerative temporomandibular joint disease
复制标题
滑液中趋化因子 RANTES 的增加及其在早期退行性颞下颌关节病中的作用
DOI：
10.1111/joor.13041
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发表时间：
2020-09-01
影响因子：
2.9
通讯作者：
Fu, Kai-Yuan
中科院分区：
文献类型：
--
作者：
Feng, Shi-Yang;Lei, Jie;Fu, Kai-Yuan
背景青少年和年轻人的颞下颌关节退行性关节病（DJD）与不可复位的关节盘移位（DDw/oR）密切相关。目的探讨DDw/oR诱发早期TMJ DJD的发病机制。方法31例12-30岁女性受试者，包括12例无DJD的DDw/oR患者，13例DDw/oR合并早期DJD患者，6例健康志愿者。使用多细胞因子阵列对受试者的滑液样本进行27种炎症相关细胞因子的筛选。通过夹心免疫测定法进一步测定了显著增加的细胞因子和破骨细胞生成的关键调节因子“核因子-κ B配体受体激活因子”（RANKL）。采用Cell Counting Kit-8、Transwell系统、抗酒石酸酸性磷酸酶染色和骨测定板评估这些因素对RAW 264.7细胞增殖、迁移、破骨细胞生成和骨吸收活性的可能病理生理作用。结果巨噬细胞源性炎性蛋白1 β（MIP 1 β）和正常T细胞活化后表达和分泌的调节因子（RANTES）与对照组相比有显著性差异。与RANKL浓度不变相反，在DDw/oR和早期DJD受试者中检测到RANTES水平显著升高。MIP-1 β浓度仅在无DJD的DDw/oR受试者中升高。在功能上，MIP-1 β和RANTES均能以浓度依赖性方式增强巨噬细胞迁移，而只有RANTES对破骨细胞形成和骨吸收活性表现出促进作用。结论趋化因子RANTES在DDw/oR诱导的早期TMJ DJD中表达显著上调，可能是破骨细胞生成的关键调节因子。
Background Degenerative joint disease (DJD) of the temporomandibular joints (TMJs) in adolescents and young adults is closely associated with disc displacement without reduction (DDw/oR). Objective This study aimed to determine the pathogenesis of early-stage TMJ DJD induced by DDw/oR. Methods 31 female subjects aged 12-30 years were enrolled, comprising 12 patients with DDw/oR without DJD, 13 with DDw/oR and early-stage DJD, and 6 healthy volunteers. The synovial fluid samples of the subjects were screened for 27 inflammatory-related cytokines using multiple cytokine array. Significantly increased cytokines and a key regulator of osteoclastogenesis "receptor activator of nuclear factor-kappa B ligand" (RANKL) were further determined by sandwich immunoassay. These factors were also assessed for the possible pathophysiologic actions on RAW264.7 cell proliferation, migration, osteoclastogenesis and bone-resorbing activity using Cell Counting Kit-8, Transwell system, tartrate-resistant acid phosphatase staining and osteo assay plates. Results Macrophage-derived inflammatory protein-1 beta (MIP-1 beta) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to vary significantly in relation to the controls. In contrast to an unchanged concentration of RANKL, a strong increase in the level of RANTES was detected in subjects with DDw/oR and early-stage DJD. MIP-1 beta concentrations were only elevated in subjects with DDw/oR without DJD. Functionally, both MIP-1 beta and RANTES could enhance macrophage migration in a concentration-dependent manner, while only RANTES exhibited a promoting effect on osteoclast formation and bone-resorbing activity. Conclusions Chemokine RANTES was significantly upregulated and might be a key regulator of osteoclastogenesis contributing to DDw/oR-induced early-stage TMJ DJD.