Matrix Metalloproteinase-2 Gene Polymorphisms Decrease Chances of Muscle TMD Development in Brazilian Population

Research Article

J Dent & Oral Disord. 2021; 7(3): 1163.

Matrix Metalloproteinase-2 Gene Polymorphisms Decrease Chances of Muscle TMD Development in Brazilian Population

Cordeiro PCF1, Bonato LL2, Quinelato V1*, Santos TAB2, Vieira AR3, Granjeiro JM4, Tesch R5, Casado PL6, Calasans-Maia JA1

1Orthodontics Department, Universidade Federal Fluminense, Dentistry School, Brazil

2School of Dentistry, Universidade Federal Fluminense, Brazil

3Departments of Oral Biology and Pediatric Dentistry, University of Pittsburgh, School of Dental Medicine, Pittsburgh, USA

4Laboratory of Clinical Research in Dentistry, Universidade Federal Fluminense, Dentistry School, Brazil

5School of Medicine of Petropolis, Brazil

6Universidade Federal Fluminense, Brazil

*Corresponding author: Valquíria Quinelato, Orthodontics Department, School of Dentistry, Universidade Federal Fluminense (Mario Santos Braga St, 30/214 - Center – Niterói-RJ, Brazil

Received: April 06, 2021; Accepted: May 06, 2021; Published: May 13, 2021


Introduction: Muscular Temporomandibular disorders or masticatory disorders are characterized by orofacial pain and functional limitations associated with oral dysfunctions, emotional changes and/or genetic factors. Matrix Metalloproteinases (MMPs) are proteolytic enzymes that constitute the extracellular matrix and play an important role in the skeletal muscle adaptation.

Objectives: To evaluate the association between polymorphisms in the Matrix Metaloprotease-2 (MMP2) gene and the presence of muscular disorders.

Methods: RDC/TMD questionnaire was applied for clinical diagnosis of Temporomandibular Disorders (TMD) in the study sample and three diagnosis groups were formed: control group (n=154), muscular TMD (n=122) and joint TMD (n=49). Genomic DNA was obtained from saliva samples and six single nucleotide polymorphisms in the MMP2 gene were selected. Results: A tendency of association between the presence of the CT genotype (rs243865) and the absence of muscular TMD was observed when compared to the control group (p=0.05). There was a significant prevalence of the polymorphic CT+TT (rs243865) genotypes in the control group (p=0.04) compared to the muscular TMD group (p=0.05). Confirming these results, TCCACC MMP2 haplotype showed higher association (p=0.01) with protection against muscular TMD.

Conclusion: Polymorphism in the MMP2 gene (rs243865) is related to protection against muscular TMD.

Keywords: Temporomandibular joint dysfunction syndrome; Polymorphism genetic; Matrix Metalloproteinase-2


Temporomandibular Disorders (TMD) collectively comprise a set of clinical conditions associated with pain and/or dysfunction located in the masticatory musculature and/or Temporomandibular Joints (TMJ) [1] with muscular disorders being the single most prevalent diagnostic group [2]. The diagnosis of muscular TMD is based on the presence of clinical signs and symptoms standardized in the form of criteria [3]. However, these patients do not evolve uniformly, many presenting disproportionate pain in response to different types of stimuli [1,2,4], as well as comorbid, regional, or systemic pain [5]. In addition, in some patients, pain complaints persist even after resolution of the initial injury [2,6].

It is currently known that chronic muscular pain, including masticatory pain, is influenced by neuronal, central, and peripheral sensitization phenomena [7], often influenced by predisposing genetic factors. The genetic influence involved in the pathophysiology of TMD has been previously demonstrated in different studies related to different genes - ESR1, ESRRB, RANK, RANKL, and OPG [6,8]. In addition to pain thresholds, the genetic profile of each patient also proved to be able to regulate muscle regenerative capacity [2].

Adult skeletal muscle tissue, including masticatory muscle, has high regenerative capacity in response to acute or chronic injuries. As skeletal muscle fibers are in their terminal stage of differentiation and therefore unable to participate in tissue repair, this response is largely attributed to a small, distinct population of myogenic progenitor cells resident in adult skeletal muscle, called Satellite Cells (SC) [9,10]. SC can be activated following chemical and mechanical stimuli, migrating to the injury site and orchestrating muscle regeneration [9]. Mature muscle fibers, in turn, produce and are involved by an Extracellular Matrix (ECM), which also acts in tissue repair through the release of specific biochemical mediators [11,12], mainly those called Matrix Metalloproteinases (MMPs).

MMPs constitute a broad heterogeneous family of enzymes responsible for breaking peptide bonds between protein amino acids [9,12]. In muscle tissue, MMP-2 and MMP-9, produced by myoblasts, fibroblasts, and endothelial cells [11,13] are prominent, creating a favorable environment for muscle repair [14]. MMPs are responsible for ECM renewal, increasing its chemotactic potential [10,15]. They are, for example, responsible for the cleavage and activation of Hepatocyte Growth Factor (HGF) [9], enabling it to bind with SC membrane receptors, such as c-Met, activating them and thus, inducing tissue repair by cell proliferation and differentiation [15]. In addition, MMP-2 is even involved in angiogenic processes after mechanical stimuli, capable of generating myofibrillar hypertrophic effects (Figure 1) [16].