Analysis of Masticatory Muscle Tendon-aponeurosis Hyperplasia by Using Next-generation Sequencing

Abstract

Background/Aim: Masticatory muscle tendonaponeurosis hyperplasia (MMTAH) is a disease associated with a mouth opening limitation. Here, we conducted a bioinformatics analysis to examine gene expression patterns in patients with MMTAH in comparison to those with facial deformity (FD). Materials and Methods: Seven MMTAH patients and three FD patients were recruited. We conducted RNA sequencing analysis, quantitative reverse transcription polymerase chain reaction and immunoblot analysis. Results: Of the identified 19,767 mapped read tags that showed clear differential expression, 2,471 genes were significantly up-regulated and 2,849 genes were significantly down-regulated in patients with MMTAH compared to those in patients with FD. Among the up-regulated genes, ten genes were significantly increased. The distribution of upregulated and down-regulated genes at different ages tended to be similar. Moreover, the protein levels of Ankyrin Repeat Domain 2, Troponin T1 and myosin heavy chain 7, which are associated with slow twitch fibers and mechanical loading, were strongly expressed in patients with MMTAH compared to those in patients with FD. Conclusion: The gene expression pattern in MMTAH patients was similar regardless of age. As the transition of fast-to-slow twitch in the skeletal muscle is induced by mechanical loading, and up-regulation of slow twitch molecules was observed in MMTAH patients, mechanical loading is suggested to be implicated in MMTAH.

Genetic Landscape of Masticatory Muscle Tendon–Aponeurosis Hyperplasia

“…The SIX protein binds to MEF3 sites in the promoters of genes and regulates their expression in myogenic cells; namely, the hypaxial Myf5 enhancer, the two MyoD enhancers, in the fast myosin heavy chain ( Myh ) locus [ 47 ]. DACH1 , which we identified in this study, can affect Myf5 and MyoD and was reported previously by Yumoto et al to be associated with MMTAH [ 21 ]. Overall, we identified several candidate genes in patients with MMTAH.…”

“…Ito et al [ 20 ] reported differences in gene expression among the masseter aponeurosis, temporal tendon, and Achilles tendon from Japanese macaque. Although there was no overlap between our candidate genes and the genes reported by Yumoto et al [ 21 ], future analysis using samples from our patients could determine whether six genes ( Mkx , Myf5 , MyoD , ANKRD2 , TNNT1 , MYH7 ) reported by Yumoto et al were upregulated in temporal tendon from our patients with MMTAH.…”

“…Furthermore, although combining the patients’ WGS results with the RNA-seq results obtained from the pig samples provided useful insights, the potential differences in physiology and genetic backgrounds between humans and pigs may influence the interpretation and applicability of our findings. Yumoto et al [ 21 ] reported differences in gene expression between temporal tendons from patients with MMTAH and temporal tendons from patients with facial deformity. Ito et al [ 20 ] reported differences in gene expression among the masseter aponeurosis, temporal tendon, and Achilles tendon from Japanese macaque.…”

“…Recently, Ito et al [ 20 ] showed that the response to mechanical stretching stress was different in the temporal tendon and the Achilles tendon. Yumoto et al [ 21 ] found that gene expression was different in the temporal tendon of patients with MMTAH and in the temporal tendon of patients with jaw deformity by RNA-seq. However, no whole genome studies of MMTAH have been conducted so far.…”

Congenital mandibular coronoid process hyperplasia and associated diseases

“…Yoda et al (2009) reported 10 cases of masticatory muscle tendon‐aponeurosis hyperplasia CPH. The etiology may be related to the down‐regulation of myosin light chain 4 (MYL4) (Nakamoto et al, 2014; Sato & Yoda, 2016; Yumoto et al, 2022). In our clinical practice, one adult female patient had masticatory muscle tendon‐aponeurosis hyperplasia accompanied by CPH and restricted mouth opening (Figure 1).…”