# Matrix Metalloproteinases and Temporomandibular Joint Disorder: A Review of the Literature
## 5 Conclusions  
Despite the high prevalence of TMD in the population, current treatment modalities tend to have a poor long-term success and few patients seek treatment [2]. The available modalities are diverse, ranging from non-invasive techniques, such as physical therapy, ultrasound, low-level laser therapy, and splints, to minimally invasive techniques, such as corticosteroid injections, arthrocentesis of the joint, with or without platelet-rich plasma or hyaluronic acid injections, and arthroscopic surgery, to invasive procedures for the more advanced stage of TMD, which include disccotomy, disc replacement, and the most invasive, total joint replacement [2; 28; 29]. It is recommended that attempts at treatment begin with non-invasive techniques and progress to invasive techniques, as risks with the invasive techniques involving open joint surgery can include facial nerve and optic lesions, transarticular and intracranial perforations, and pre-auricular hematoma, among others [3]. Further limitations and complications of arthroscopy, arthrocentesis, and orthognathic surgery used for treatment of TMD include arteriovenous fistula, pseudoaneurysm, infection, broken instruments in the joint, and condylar resorption [30; 31]. Additionally, bruxism and dysfunctional oral habits have been shown to be risk factors for recurrent TMD symptoms after orthognathic surgery [32]. Due to limitations and complications of surgery, it is necessary to develop more efficacious techniques in non-invasive and pharmaceutical therapies for treating TMD. Some of the pharmaceutical therapies for TMD include botox and cyclohexaprine, which induce muscle relaxation, NSAIDs, and corticosteroids, which reduce pain and inflammation, and tricyclic antidepressants, which work to reduce pain [33]. However, these agents work to target the effects that TMD has on the patient rather than an underlying cause. To the researchers' knowledge, there are currently no pharmaceutical agents that are used to target an element of the underlying pathogenesis of TMD, such as MMPs, to stop the progression of this debilitating disorder. There is ongoing pharmaceutical research to uncover potential MMP inhibitors for therapeutic use in different disease processes, such as cancer [34]. Thus far, however, limitations have prevented identification of a suitable therapeutic agent. The poorly understood specificity of their biological substrates makes it difficult to target specific MMPs, which causes detrimental problems, as MMPs are vital to survival [34]. There have been additional problems in its use, some of which include problems with oral bioavailability, toxicity, and metabolic stability [34; 35]. Despite the unsuccessful attempts, knowledge of MMPs continues to evolve and the use of new and future technological advances, including use of CRISPR-_Cas9_ and MMP-activatable optical probes, make the use of MMP as a pharmaceutical target more hopeful [34; 35]. If and when a successful pharmaceutical agent is discovered targeting MMPs, having a good understanding of the specific MMPs involved in TMD progression could provide an expedited route to applying the therapy to TMD treatment. More studies with larger sample sizes are needed to analyze the involvement of specific MMPs in TMD. With more concrete evidence of its role, and because of the nature of the enzymes, MMPs could prove to provide a better understanding of the progression of TMD and be a valuable pharmaceutical target for therapy. Conceptualization, F.d.A.C. and L.E.A. ; Methodology, L.H., A.H.; Software, Not applicable; Validation, L.E.A., L.H., and A.H.; Formal Analysis, Not applicable; Investigation, L.H., A.H. and F.d.A.C. ; Resources, L.H., A.H.; Data Curation, L.H., A.H.; Writing--Original Draft Preparation, L.H., A.H.; Writing--Review & Editing, L.E.A., L.H., A.H., F.d.A.C. and L.T. ; Visualization, L.E.A. ; Supervision, F.d.A.C., L.T. and L.E.A. ; Project Administration, L.E.A. ; Funding Acquisition, Not applicable. This research received no external funding.