Tratamento da osteoartrite da articulação temporomandibular: revisão sistemática e avaliação dos efeitos da sinvastatina sobre osteoblastos humanos in vitro

Abstract

Osteoarthritis of the temporomandibular joint (TMJ-OA) is a chronic, non-infectious, focal degenerative disease associated with subchondral bone remodeling with functional dysregulation of osteoblasts. Studies suggest that statins are promising candidates for new drugs for osteoarthritis (OA) because of their effects on modulating the inflammatory response. Therefore, the present study aimed to carry out a systematic review in order to answer which drugs would be available for the treatment of OA. Furthermore, we also sought to use an experimental approach to evaluate the in vitro effects of simvastatin on human osteoblasts, an important cellular component involved in the pathogenesis of TMJ-OA. For the systematic review, search strategies were used in the MEDLINE, Cochrane Central, Web of Science, BBO and EMBASE databases, including articles until July 2022. After analyzing the abstracts and applying the eligibility criteria, 6 studies met the established criteria. The methodological assessment was performed using the Jadad Scale, the analysis for risk of bias was determined by the table for risk of bias, and analysis of evidence was determined by the GRADE tool. The analysis of the studies revealed that pharmacological treatment with intra-articular injections of platelet-rich plasma, triamcinolone, betamethasone, tenoxicam, hyaluronic acid, associated or not with oral glucosamine, and sodium hyaluronate, associated or not with oral glucosamine, caused a decreased pain intensity in all studies evaluated, with emphasis on the high level of evidence according to the GRADE tool for intra-articular treatment with sodium hyaluronate associated with oral glucosamine therapy. In the experimental approach of the present study, a human osteoblast lineage MG-63 was used to evaluate in vitro the effects of simvastatin. Our results demonstrated that concentrations of 1-10 μM of simvastatin did not affect the cell viability of osteoblasts. When evaluating the morphology of osteoblasts, 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, LPS-stimulated production of nitric oxide by osteoblasts was 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 TMJ-OA. 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 TMJ-OA is emphasized. Therefore, together with what is described in the literature, simvastatin appears to be a promising candidate for a drug that modulates some osteoblast functions, indicating potential for clinical use in TMJ-OA.