Center for TMD & Orofacial Pain, Peking University School & Hospital of Stomatology, Beijing, China.
National Clinical Research Center for Oral Diseases, Beijing, China.
J Oral Rehabil. 2020 Sep;47(9):1150-1160. doi: 10.1111/joor.13041. Epub 2020 Jul 13.
Degenerative joint disease (DJD) of the temporomandibular joints (TMJs) in adolescents and young adults is closely associated with disc displacement without reduction (DDw/oR).
This study aimed to determine the pathogenesis of early-stage TMJ DJD induced by DDw/oR.
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-κB 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.
Macrophage-derived inflammatory protein-1 beta (MIP-1β) 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-1β concentrations were only elevated in subjects with DDw/oR without DJD. Functionally, both MIP-1β 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.
Chemokine RANTES was significantly upregulated and might be a key regulator of osteoclastogenesis contributing to DDw/oR-induced early-stage TMJ DJD.
青少年和年轻成人的颞下颌关节（TMJ）退行性关节病（DJD）与关节盘不可复性前移位（DDw/oR）密切相关。
本研究旨在确定由 DDw/oR 引起的早期 TMJ DJD 的发病机制。
共纳入 31 名 12-30 岁的女性受试者，包括 12 名无 DJD 的 DDw/oR 患者、13 名早期 DJD 伴 DDw/oR 患者和 6 名健康志愿者。采用多细胞因子阵列对受试者的滑膜液样本进行 27 种炎症相关细胞因子的筛选。进一步通过夹心免疫测定法测定显著增加的细胞因子和破骨细胞生成的关键调节剂“核因子-κB 受体激活物配体”（RANKL）。通过细胞计数试剂盒-8、Transwell 系统、抗酒石酸酸性磷酸酶染色和骨吸收活性测定板，评估这些因子对 RAW264.7 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。
发现巨噬细胞来源的炎症蛋白-1β（MIP-1β）和活化正常 T 细胞表达和分泌的调节因子（RANTES）与对照组相比变化显著。与 RANKL 浓度不变相反，在 DDw/oR 伴早期 DJD 患者中检测到 RANTES 水平明显增加。仅在无 DJD 的 DDw/oR 患者中检测到 MIP-1β 浓度升高。功能上，MIP-1β 和 RANTES 均可浓度依赖性地增强巨噬细胞迁移，而仅 RANTES 对破骨细胞形成和骨吸收活性具有促进作用。
趋化因子 RANTES 显著上调，可能是导致 DDw/oR 引起的早期 TMJ DJD 的破骨细胞生成的关键调节剂。
