Monasterio G, Castillo F, Rojas L, Cafferata E A, Alvarez C, Carvajal P, Núñez C, Flores G, Díaz W, Vernal R
Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
Faculty of Dentistry, Universidad Peruana Cayetano Heredia, Lima, Perú.
J Oral Rehabil. 2018 Aug;45(8):589-597. doi: 10.1111/joor.12649. Epub 2018 May 30.
It is well accepted that the presence of cytokines belonging to the Th1/Th17/Th22 axis of immuno-inflammatory response in the joint environment, such as IL-1β, IL-17 and IL-22, respectively, are associated with pathogenesis of several synovial joint degenerative disorders. During temporomandibular joint osteoarthritis (TMJ-OA), IL-1β and IL-17 have been implicated in the inflammation and resorption of sub-chondral bone; however, the role of Th22 response in the TMJ-OA pathophysiology has not been established. This study aimed to compare the expression of Th1/Th17/Th22-type cytokines, chemokines and chemokine receptors in synovial fluid samples obtained from TMJ-OA or disk displacement with reduction (DDWR) patients. In addition, it aimed to associate these levels with joint pain, imagenological signs of bone degeneration, RANKL production, osteoclastogenesis and osteoclast-induced bone resorption. Higher levels of IL-1β, IL-17 and IL-22 were expressed in TMJ-OA compared with DDWR subjects, and these increased levels significantly correlated with RANKL expression, joint pain and articular bone degeneration. Higher levels of CCR5, CCR6 and CCR7, as well as their respective ligands CCL5 and CCL20, responsible for recruitment of IL-1β, IL-17 and IL-22-producing cells, were over-expressed in TMJ-OA compared with DDWR subjects. Osteoclastogenesis and osteoclast-induced bone resorption were significantly greater in presence of synovial fluid from TMJ-OA compared with DDWR subjects. These data demonstrate that cytokines, CCLs and CCRs associated with the Th1/Th17/Th22 axis of immuno-inflammatory response are involved in TMJ-OA pathogenesis. These findings suggest that IL-22 is involved in the RANKL expression in TMJ-OA, which in turn induces differentiation of osteoclasts and subsequent resorption of sub-chondral bone.
免疫炎症反应的Th1/Th17/Th22轴的细胞因子存在于关节环境中，如IL-1β、IL-17和IL-22，分别与几种滑膜关节退行性疾病的发病机制相关，这一点已被广泛接受。在颞下颌关节骨关节炎（TMJ-OA）中，IL-1β和IL-17与软骨下骨的炎症和吸收有关；然而，Th22反应在TMJ-OA病理生理学中的作用尚未明确。本研究旨在比较从TMJ-OA或可复性盘移位（DDWR）患者获得的滑液样本中Th1/Th17/Th22型细胞因子、趋化因子和趋化因子受体的表达。此外，旨在将这些水平与关节疼痛、骨退化的影像学征象、RANKL产生、破骨细胞生成以及破骨细胞诱导的骨吸收相关联。与DDWR受试者相比，TMJ-OA中IL-1β、IL-17和IL-22的表达水平更高，且这些升高的水平与RANKL表达、关节疼痛和关节骨退化显著相关。与DDWR受试者相比，TMJ-OA中负责募集产生IL-1β、IL-17和IL-22细胞的CCR5、CCR6和CCR7及其各自的配体CCL5和CCL20表达上调。与DDWR受试者相比，TMJ-OA滑液存在时破骨细胞生成和破骨细胞诱导的骨吸收明显更强。这些数据表明，与免疫炎症反应的Th1/Th17/Th22轴相关的细胞因子、CCL和CCR参与了TMJ-OA的发病机制。这些发现表明，IL-22参与了TMJ-OA中RANKL的表达，进而诱导破骨细胞分化以及随后软骨下骨的吸收。
