Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males

Smith, Shad B.; Parisien, Marc; Bair, Eric; Belfer, Inna; Chabot-Doré, Anne Julie; Gris, Pavel; Khoury, Samar; Tansley, Shannon; Torosyan, Yelizaveta; Zaykin, Dmitri V.; Bernhardt, Olaf; Serrano, Priscila de Oliveira; Gracely, Richard H.; Jain, Deepti; Järvelin, Marjo Riitta; Kaste, Linda M.; Kerr, Kathleen F.; Kocher, Thomas; Lähdesmäki, Raija; Laniado, Nadia; Laurie, Cecelia; Männikkö, Minna; Meloto, Carolina B.; Nackley, Andrea G.; Nelson, Sarah C.; Pesonen, Paula; Ribeiro-Dasilva, Margarete; Rizzatti-Barbosa, Célia Marisa; Sanders, Anne E.; Schwahn, Christian; Sipilä, Kirsi; Sofer, Tamar; Teumer, Alexander; Mogil, Jeffrey S.; Fillingim, Roger B.; Greenspan, Joel D.; Ohrbach, Richard; Slade, Gary D.; Maixner, William; Diatchenko, Luda

doi:10.1097/j.pain.0000000000001438

Cited by 40 publications

(33 citation statements)

References 48 publications

(51 reference statements)

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“…38 More recently, the OPPERA researchers pooled two separate cohorts of TMD patients and controls and found a 2.9 times increased odds of TMD in men (but not women) possessing an SNP in chromosome 3 that decreases expression of the muscle RAS oncogene homolog gene, which is involved in cell growth and differentiation processes. 25 These findings were nominally replicated in the researchers' meta-analysis of seven other TMD cohorts but were not statistically significant. 25 Genome-wide association studies suggest that genetic and epigenetic factors may be implicated in chronic widespread pain conditions, such as fibromyalgia, that often overlap with TMD.…”

Section: Pre-diagnosismentioning

confidence: 95%

“…25 These findings were nominally replicated in the researchers' meta-analysis of seven other TMD cohorts but were not statistically significant. 25 Genome-wide association studies suggest that genetic and epigenetic factors may be implicated in chronic widespread pain conditions, such as fibromyalgia, that often overlap with TMD. Potential candidate genes identified include SLC64A4, TRPV2, MYT1L, and NRXN3.…”

Section: Pre-diagnosismentioning

confidence: 95%

“…24 Such TMD cohorts have allowed researchers to pool resources internationally and explore a variety of potential biomarkers, such as genetic and psychophysical associations in TMD. 25,26 For TN, no similar cohorts exist, and the relatively low incidence of TN (about 4 in 100,000) 27 One of the most widely studied genetic biomarkers in facial pain is catechol-O-methyltransferase (COMT) in TMD. COMT encodes a ubiquitous enzyme responsible for the metabolism of catecholamines, which include the neurotransmitters dopamine, epinephrine, and norepinephrine.…”

Section: Pre-diagnosismentioning

confidence: 99%

See 2 more Smart Citations

Biomarkers in temporomandibular disorder and trigeminal neuralgia: A conceptual framework for understanding chronic pain

Doshi

Nixdorf

Campbell

et al. 2020

Canadian Journal of Pain

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In this review, we will explore the use of biomarkers in chronic pain, using the examples of two prototypical facial pain conditions: trigeminal neuralgia and temporomandibular disorder. We will discuss the main categories of biomarkers and identify various genetic/genomic, molecular, neuroradiological, and psychophysical biomarkers in both facial pain conditions, using them to compare and contrast features of neuropathic, nonneuropathic, and mixed pain. By using two distinct model facial pain conditions to explore pain biomarkers, we aim to familiarize readers with different types of biomarkers currently being studied in chronic pain and explore how these biomarkers may be used to develop new precision medicine approaches to pain diagnosis, prognosis, and management. RÉSUMÉ Dans cette revue, nous examinerons l'utilisation de biomarqueurs dans la douleur chronique, en utilisant les exemples de deux affections prototypiques de douleur faciale : la névralgie du trijumeau et le trouble temporomandibulaire. Nous discuterons des principales catégories de biomarqueurs et identifierons divers biomarqueurs géétiques/génomiques, moléculaires, neuroradiologiques et psychophysiques pour ces deux pathologies, en les utilisant pour comparer et distinguer les caractéristiques de la douleur neuropathique, non neuropathique et mixte. En utilisant deux modèles distincts de douleur faciale pour explorer les biomarqueurs de la douleur, nous visons à familiariser les lecteurs avec différents types de biomarqueurs actuellement étudiés dans la douleur chronique et à examiner comment ces biomarqueurs peuvent être utilisés pour développer de nouvelles approches de médecine de précision pour le diagnostic, le pronostic et la prise en charge de la douleur.

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Section: Pre-diagnosismentioning

confidence: 95%

Section: Pre-diagnosismentioning

confidence: 95%

Section: Pre-diagnosismentioning

confidence: 99%

See 1 more Smart Citation

Biomarkers in temporomandibular disorder and trigeminal neuralgia: A conceptual framework for understanding chronic pain

Doshi

Nixdorf

Campbell

et al. 2020

Canadian Journal of Pain

View full text Add to dashboard Cite

show abstract

“…Another possible mechanism by which TMJ OA may arise is from alterations in the ECM; this might be due to genetic disturbances that directly alter the composition of the ECM in the TMJ, or indirectly due to changes in composition and/or turnover of the ECM caused by other genetic factors. Several genes are associated with the painful TMJ disorder as discovered by a genome-wide association study (GWAS) [48]. In a recent GWAS study, 22 independent loci were found that showed an implicit association with degenerative bone changes in the TMJ [49].…”

Section: Genetic Factorsmentioning

confidence: 99%

Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis

Lee

Park

Auh

et al. 2020

IJMS

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Exosomes are nanosized vesicles (30–140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, which, in addition to chronic pain, is characterized by progressive cartilage breakdown, condylar bone remodeling, and synovitis. However, traditional clinical treatments have limited symptom- and structure-modifying effects to restore damaged cartilage and other TMJ tissues. This is due to the limited self-healing capacity of condylar cartilage. Recently, stem-cell-derived exosomes have been studied as an alternative therapeutic approach to tissue repair and regeneration. It is known that trophic regulation of mesenchymal stem cells (MSCs) has anti-inflammatory and immunomodulatory effects under pathological conditions, and research on MSC-derived exosomes is rapidly accumulating. MSC-derived exosomes mimic the major therapeutic effects of MSCs. They affect the activity of immune effector cells and possess multilineage differentiation potential, including chondrogenic and osteogenic differentiation. Furthermore, exosomes are capable of regenerating cartilage or osseous compartments and restoring injured tissues and can treat dysfunction and pain caused by TMJ OA. In this review, we looked at the uniqueness of TMJ, the pathogenesis of TMJ OA, and the potential role of MSC-derived exosomes for TMJ cartilage and bone regeneration.

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“…Regarding the TMJ, a recent study identified genetic variations associated with temporomandibular disorders. This lead to the identification of a specific molecular pathway that plays a role its pathophysiology (Smith et al, 2019). The emerging accessibility of genetic testing with techniques such as comparative genome hybridization arrays and whole- or targeted-exome sequencing will provide further insight into this matter.…”

Section: Condylar Resorptionmentioning

confidence: 99%

The Biomechanical Effect of the Sagittal Split Ramus Osteotomy on the Temporomandibular Joint: Current Perspectives on the Remodeling Spectrum

et al. 2019

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The sagittal split ramus osteotomy is a key approach for treating dentofacial deformities. Although it delivers excellent results, the sagittal split ramus osteotomy is believed to induce stress to the temporomandibular joint. Potential stress inducers could be classified as intra- and postoperative factors resulting in an inflammatory response and molecular cascades, which initiate physiological remodeling. Occasionally, this process exceeds its capacity and causes pathological remodeling, through either degenerative joint disease or condylar resorption. Hard evidence on how orthognathic surgery causes inflammation and how this inflammation is linked to the spectrum of remodeling remains scarce. Current concepts on this matter are mainly based on clinical observations and molecular mechanisms are extrapolated from fundamental research in other body parts or joints. This perspective study provides an overview of current knowledge on molecular pathways and biomechanical effects in temporomandibular joint remodeling. It provides research directions that could lead to acquiring fundamental evidence of the relation of orthognathic surgery and inflammation and its role in remodeling. Performing osteotomies in animal models and identifying inflammatory mediators as well as their effect on the joint seem promising. Patients affected by pathological remodeling can also provide samples for histological as well as molecular analysis. Individual susceptibility analysis by linking certain suspect phenotypes to genetic variation could identify the cause and molecular pathway responsible for degenerative joint disease and condylar resorption, ultimately leading to clinically applicable treatment and prevention strategies.

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Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males

Abstract: Supplemental Digital Content is Available in the Text. A polymorphic locus associated with a protective effect against painful temporomandibular disorder in males regulates the expression of the muscle RAS oncogene homolog ( MRAS ) gene.

Cited by 40 publications

References 48 publications

Biomarkers in temporomandibular disorder and trigeminal neuralgia: A conceptual framework for understanding chronic pain

Biomarkers in temporomandibular disorder and trigeminal neuralgia: A conceptual framework for understanding chronic pain

Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis

The Biomechanical Effect of the Sagittal Split Ramus Osteotomy on the Temporomandibular Joint: Current Perspectives on the Remodeling Spectrum

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