Condyle cartilage defect can hardly self-heal, which is related to inflammation. Pyroptosis participates chronic inflammation, so we hypothesized that pyroptosis might exist in TMJOA. Our research proved that IL-1β, IL-18, NLRP3 and CASP1 were higher expressed in degenerative TMJOA synovial fluid, which were consistent with pyroptosis molecules. Thus, pyropyosis of chondrocytes or synovial cells may be exist in condylar degeneration. Current data also indicated that HA protected condylar from progressive degradation by means of relieving clinical symptoms and decreasing some pyroptosis molecules. These results provide a basis for further study on the mechanism of TMJOA.
Inflammation is a signal in progressive articular tissue damage. Previous studies have shown that the expressions of inflammatory mediators included interleukin (IL), matrix metalloproteinase (MMP) and prostaglandin E2 (PGE2) in the synovial fluid of OA patients are higher than that of the normal [12, 13]. Besides, inflammation also breaks down the catabolism of matrix and leads deterioration of internal environment. Specific anti-inflammation therapy may provide a new clue to prevent cartilage from damaging. Meanwhile, pyroptosis is the highlighted topic in inflammation disease recently, which can connect with cartilage degradation scientifically because its inflammation essence. Osseous changes generally occur in response to TMJ inflammation while CBCT image shows hard-tissues clearly [14, 15]. Our research is scientific in grouping according to CBCT or MRI to distinguish condylar destruction accurately.
IL-1β and IL-18 are cell lysis products in cell pyroptosis, participating a series of inflammatory and autoimmune diseases, these two cytokines can amplify inflammation through multiple pathways and contribute to the occurrence of pyroptosis [16–18]. Some studies have proved a higher expression on IL-1β in TMJOA, However, IL-18 was reported rarely. Our study are consistent with above studies at higher concentration of IL-1β and justified a new result of higher IL-18 concentration. NLRP3, one of the most specific upstream signal protein in cell pyroptosis, participating canonical inflammasome of pyroptosis mediated by CASP1, then eliciting plasma membrane pore formation, mitochondrial dysfunction and lysosomal rupture. A study revealed collagen-induced arthritis had a high expression of NLRP3, anti-inflammatory therapy targeting NLRP3 might become a new method for the treatment of OA [19]. Moreover, Synovial inflammation is closely related to NLRP3 and CASP1 [20], Pyroptosis of synovial fibroblasts in knee osteoarthritis mediates synovial inflammation. But the cytological mechanism of temporomandibular joint may be different from primary knee joint because its special structure charts included fibrous layer. Thus, we explore pyroptosis in temporomandibular joint with its unique fibrocartilage structure in this research. Despite of a low positive concentration of NLRP3 in two groups, but higher concentrations on IL-1β, IL-18, NLRP3 and CASP1 in TMJOA patients compared with TMJID patients provided possibility to pyroptosis.
The occurrence of pyroptosis depends on a precise signal regulation, it does not occur unless the DAMPs or PAMPs were stimulated, intracellular signal is activated subsequently, DAMPs as endogenous molecular structures released to extracellular environment through tissue injury or hypoxia stimulation, participate canonical pathway of pyroptosis controlled by CASP1[21]. PAMPs comprise molecular structures that are found in microbes included lipopolysaccharide (LPS), which can take part in canonical and non-canonical pathway of pyroptosis controlled by CASP1 or CASP-4/5/11. A recent study proved that the expression of CASP1 increased significantly in knee osteoarthritis cartilage compared with normal cartilage tissue. TMJ is a rotating-hinge joint, which is suitable for occlusal mechanical environment, so we believed that DAMPs were main stimulation because temporomandibular joint lived in a sterile environment and accepted with biomechanical stimulation such as stress, fluid shear stress transmitted by abnormal occlusal contact. Previous reports indicated unilateral anterior crossbite model built in sprague-dawley (SD) rats could induce OA lesions via apoptosis or necrosis of chondrocytes and matrix loss [22]. In this study, the malocclusion is most probably source of DAMPs because all patients in two groups were accompanied with oral malocclusion.
Additionally, We tried to evaluate therapeutic effect of twice HA injection therapy on pyroptosis molecules. Application of HA as empirical intra-articular injection plays an important role in the protection, nutrition and function of joints [23]. HA also regulates electrolyte and water in extracellular fluid, lubricates joints, resists infection. Our current research also verified its anti-inflammatory effect due to a relieved symptoms and decreased concentrations of IL-1β, IL-18, NLRP3. Although there is no statistical significance on concentration of CASP1 between twice HA injections, which may be because a short time of follow-up can not establish a complete immune mechanism.
Currently, Targeted drug therapy tends to be mature. Inhibitor therapy targeting above pyroptosis molecules may become a new resolution for progressive osteoarthritis once mechanical stress can not be relieved immediately, which also makes individualized articular joint destruction treatment posssible.
In conclusion, pyroptosis related molecules were higher expressed in OA patients. pyroptosis of chondrocytes or synovial cells might be a new reason for cartilage degradation, and empirical HA’ intra-articular injection was effective in reliving clinical symptoms and decreasing some inflammatory factors.