Gene expression profiling of the masticatory muscle tendons and Achilles tendons under tensile strain in the Japanese macaque Macaca fuscata

Abstract

Both Achilles and masticatory muscle tendons are large load-bearing structures, and excessive mechanical loading leads to hypertrophic changes in these tendons. In the maxillofacial region, hyperplasia of the masticatory muscle tendons and aponeurosis affect muscle extensibility resulting in limited mouth opening. Although gene expression profiles of Achilles and patellar tendons under mechanical strain are well investigated in rodents, the gene expression profile of the masticatory muscle tendons remains unexplored. Herein, we examined the gene expression pattern of masticatory muscle tendons and compared it with that of Achilles tendons under tensile strain conditions in the Japanese macaque Macaca fuscata. Primary tenocytes isolated from the masticatory muscle tendons (temporal tendon and masseter aponeurosis) and Achilles tendons were mechanically loaded using the tensile force and gene expression was analyzed using the next-generation sequencing. In tendons exposed to tensile strain, we identified 1076 differentially expressed genes with a false discovery rate (FDR) < 10−10. To identify genes that are differentially expressed in temporal tendon and masseter aponeurosis, an FDR of < 10−10 was used, whereas the FDR for Achilles tendons was set at > 0.05. Results showed that 147 genes are differentially expressed between temporal tendons and masseter aponeurosis, out of which, 125 human orthologs were identified using the Ensemble database. Eight of these orthologs were related to tendons and among them the expression of the glycoprotein nmb and sphingosine kinase 1 was increased in temporal tendons and masseter aponeurosis following exposure to tensile strain. Moreover, the expression of tubulin beta 3 class III, which promotes cell cycle progression, and septin 9, which promotes cytoskeletal rearrangements, were decreased in stretched Achilles tendon cells and their expression was increased in stretched masseter aponeurosis and temporal tendon cells. In conclusion, cyclic strain differentially affects gene expression in Achilles tendons and tendons of the masticatory muscles.

Genetic Landscape of Masticatory Muscle Tendon–Aponeurosis Hyperplasia

“…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. 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.…”

“…To elucidate the environmental factors of this disease, Hayashi et al [ 18 , 19 ] examined the effect of cyclic stretch on tenocytes and found that the expression of CRYBA4 mRNA was increased and the abundance of the decorin protein was increased via the yes-associated protein. 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.…”

“…Acquired factors, such as gliding and clenching, can have the same effect on the masticatory tendons. Indeed, Sato, Yoda, and coworkers [ 17 , 18 , 19 ] demonstrated that the pathogenesis of MMTAH was dependent on environmental factors and that the cyclic strain differentially affected the gene expression in the Achilles tendon and tendons of the masticatory muscles [ 20 ]. Moreover, hyperplasia always develops bilaterally, and MMTAH is more common in women than in men [ 8 , 18 ].…”