Treatment of temporomandibular joint osteoarthritis: systematic review of the literature and evaluation of the effects of simvastatin on human osteoblasts in vitro
Drug Therapy. Osteoarthritis. Temporomandibular Joint. Simvastatin. Osteoblasts.
Osteoarthritis of the temporomandibular joint (TMJ-OA) is a chronic, non-infectious, focal degenerative disease associated with the subchondral bone remodeling with functional dysregulation of osteoblasts. Recent studies suggest that statins are promising candidates for new drugs for osteoarthritis due to their effects on modulating the inflammatory response. Therefore, the present study aimed to carry out a systematic review of the scientific literature in order to answer which drugs would be available for the treatment of osteoarthritis, and then, an experimental evaluation was carried out in order to characterize the in vitro effects of simvastatin on human osteoblasts. Initially, search strategies were used in the MEDLINE, Cochrane Central, Web of Science, BBO and EMBASE databases until June 2021 and search for the so-called "gray literature" in the Open-GRAY database. After analyzing the abstracts, and applying the inclusion and exclusion criteria, 6 studies met the established eligibility criteria. The methodological evaluation was performed using the Jadad Scale and the analysis regarding the risk of bias was determined by the Table for Risk of Bias, and analysis of the evidence was determined by the GRADE tool. The results of this phase revealed a decrease in pain intensity in all included studies, as well as a reduction in TMJ noise in 50% of clinical studies with patients with OA. These data indicate that pharmacologically treated groups had slightly better outcomes than placebo groups. The experimental part of the present work used the human cell line MG-63 to evaluate the effects of simvastatin. In this step, we initially sought to evaluate the cell viability of MG-63 cells by the MTT assay after exposure to simvastatin for 24 hours. Our results demonstrated that concentrations of 1-10 μM of simvastatin did not affect the cell viability of MG-63 cells. Then, when the morphology of the osteoblasts was evaluated, it was observed that simvastatin altered the morphology of the cells as the polarized shape was replaced by an increase in the number of cells with a rounded profile. This change in morphology was also observed when cells were stimulated with LPS. However, when evaluating the phagocytic capacity of these cells, treatment with simvastatin was not able to induce/alter the phagocytosis of zymosan particles. In another experimental set, the production of nitric oxide by MG-63 cells stimulated by LPS was significantly inhibited by treatment with simvastatin. Taken together, the results of this study demonstrate that the scientific literature gathered in the systematic review presents therapeutic alternatives that support the improvement of pain and noise in OA-TMJ. However, studies with detailed standardized variables and methods are necessary in order to reduce the risk of bias found, which may compromise the conclusion of a certain therapeutic option for clinical practice. Furthermore, the importance of the correlation of clinical studies with biomarkers evaluated in vitro that can contribute to the analysis of drugs aiming at the prevention and/or stagnation of the progression of OA-ATM is emphasized. Therefore, we demonstrated in vitro that simvastatin proved to be a promising candidate for a drug that modulates some osteoblast functions, indicating a potential for clinical use in OA-ATM.