Effect of Postnatal Myostatin Inhibition on Bite Mechanics in Mice.

Stéphane J Montuelle,Susan H Williams,Vincent Mouly,Nicholas R Lozier,Sonsoles De Lacalle

doi:10.1371/journal.pone.0134854

Abstract

As a negative regulator of muscle size, myostatin (Mstn) impacts the force-production capabilities of skeletal muscles. In the masticatory system, measures of temporalis-stimulated bite forces in constitutive myostatin KOs suggest an absolute, but not relative, increase in jaw-muscle force. Here, we assess the phenotypic and physiologic impact of postnatal myostatin inhibition on bite mechanics using an inducible conditional KO mouse in which myostatin is inhibited with doxycycline (DOX). Given the increased control over the timing of gene inactivation in this model, it may be more clinically-relevant for developing interventions for age-associated changes in the musculoskeletal system. DOX was administered for 12 weeks starting at age 4 months, during which time food intake was monitored. Sex, age and strain-matched controls were given the same food without DOX. Bite forces were recorded just prior to euthanasia after which muscle and skeletal data were collected. Food intake did not differ between control or DOX animals within each sex. DOX males were significantly larger and had significantly larger masseters than controls, but DOX and control females did not differ. Although there was a tendency towards higher absolute bite forces in DOX animals, this was not significant, and bite forces normalized to masseter mass did not differ. Mechanical advantage for incisor biting increased in the DOX group due to longer masseter moment arms, likely due to a more anteriorly-placed masseter insertion. Despite only a moderate increase in bite force in DOX males and none in DOX females, the increase in masseter mass in males indicates a potentially positive impact on jaw muscles. Our data suggest a sexual dimorphism in the role of mstn, and as such investigations into the sex-specific outcomes is warranted.

Highlights

The protein myostatin (Mstn) is a member of the TGF-8 beta family that negatively regulates muscle size
Postnatal Myostatin Inhibition and Bite Mechanics in Mice myostatin may not alter the absolute force-generating capacity in some muscles, and in others, it may result in a decrease in force relative to muscle size [4–6]
We focused on within-sex comparisons for these analyses, rather than the sex by treatment interaction, because we were interested primarily in the biomechanical basis of potential differences in bite force

Summary

Introduction

The protein myostatin (Mstn) is a member of the TGF-8 beta family that negatively regulates muscle size. Stimulation of the temporalis to tetanus in anesthetized Mstn KOs results in significantly larger absolute (but not relative) bite forces compared to controls [7–10]. An increase in temporalis size in Mstn-deficient mice is accompanied by an increase in the proportion of type II myofibers and, contrary to limb muscles, show a decrease in type II fiber diameter [7]. These data, coupled with morphologic findings for the skull in Mstn-/- mice (e.g., shorter crania, longer and rounder mandibles), provide further evidence of an altered craniofacial loading environment due to Mstn deficiency [8–14]. Endocranial volume and brain size are significantly reduced in Mstn-/- mice, which has been interpreted as a potential influence of masticatory muscle hypertrophy on brain growth [10]

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