Muscle-Bone Crosstalk in the Masticatory System: From Biomechanical to Molecular Interactions

Abstract

The masticatory system is a complex and highly organized group of structures, including craniofacial bones (maxillae and mandible), muscles, teeth, joints, and neurovascular elements. While the musculoskeletal structures of the head and neck are known to have a different embryonic origin, morphology, biomechanical demands, and biochemical characteristics than the trunk and limbs, their particular molecular basis and cell biology have been much less explored. In the last decade, the concept of muscle-bone crosstalk has emerged, comprising both the loads generated during muscle contraction and a biochemical component through soluble molecules. Bone cells embedded in the mineralized tissue respond to the biomechanical input by releasing molecular factors that impact the homeostasis of the attaching skeletal muscle. In the same way, muscle-derived factors act as soluble signals that modulate the remodeling process of the underlying bones. This concept of muscle-bone crosstalk at a molecular level is particularly interesting in the mandible, due to its tight anatomical relationship with one of the biggest and strongest masticatory muscles, the masseter. However, despite the close physical and physiological interaction of both tissues for proper functioning, this topic has been poorly addressed. Here we present one of the most detailed reviews of the literature to date regarding the biomechanical and biochemical interaction between muscles and bones of the masticatory system, both during development and in physiological or pathological remodeling processes. Evidence related to how masticatory function shapes the craniofacial bones is discussed, and a proposal presented that the masticatory muscles and craniofacial bones serve as secretory tissues. We furthermore discuss our current findings of myokines-release from masseter muscle in physiological conditions, during functional adaptation or pathology, and their putative role as bone-modulators in the craniofacial system. Finally, we address the physiological implications of the crosstalk between muscles and bones in the masticatory system, analyzing pathologies or clinical procedures in which the alteration of one of them affects the homeostasis of the other. Unveiling the mechanisms of muscle-bone crosstalk in the masticatory system opens broad possibilities for understanding and treating temporomandibular disorders, which severely impair the quality of life, with a high cost for diagnosis and management.

Keywords: bone biomechanical; craniofacial bones; masticatory muscles; musculoskeletal system; paracrine communication.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with the authors SB, JB-M.

Copyright © 2021 Buvinic, Balanta-Melo, Kupczik, Vásquez, Beato and Toro-Ibacache.

Figures

Figure 1

Particularities of masticatory muscles with respect to that of the trunk and limbs. Differences between trunk and limb muscles (left panels) and masticatory muscles (right panels) are depicted, as indicated at the top of the figure. (A) While the trunk and limb muscles form from the mesoderm-derived somites, the masticatory muscles are derived from mesodermic-derived cells at the first pharyngeal arch (origin sites colored in dark-brown). (B) The trunk and limb muscles express myosin heavy chains (MyHC) type I, IIA, or IIX. Each myofiber expresses a single type of MyHC, and type II fast-fibers have a larger diameter than type I slow-fibers. In masticatory muscles, apart from the classic MyHC types (I, IIA, IIX), the neonatal and cardiac (atrial) types are expressed. There is a large proportion of “hybrid” fibers, simultaneously expressing several MyHCs types. This means that the fibers can have great force-generating properties, with high resistance to fatigue. Additionally, in masticatory muscles, type I fibers are larger in diameter than type II. (C) In masticatory muscles, type I myofibers are even 10-fold slower than in trunk and limbs. Moreover, the velocity of shortening of type II myofibers is faster in masticatory muscles as compared to the trunk and limbs ones.

Figure 2

Particularities of the mandibular bone with respect to the trunk and limb bones. Differences between long bones of the appendicular skeleton (left panels) and mandible (right panels) are depicted, as indicated at the top of the figure. (A) While long bones derive from embryonic mesoderm, mandibular bone derives from cells of the 1st pharyngeal arch coming from the neural crest (origin sites colored in dark-brown). (B) Mandible is the only structure supporting the four main mineralized tissues: bone, cartilage, enamel, and dentin. Instead, long bones only have bone and cartilage. Because jaws support the teeth, they are exposed to additional developmental processes until adulthood and undergo pathologies that are not present in other bones. (C) While long bones contain both red and yellow bone marrow, the jaws mainly have red bone marrow. (D) Mesenchymal stem cells (MSC) derived from mandible have better osteogenic potential than derived from long bones; they have a higher proliferation rate and mineralization, with an increased regeneration capacity. OB: osteoblasts.

Figure 3

Schematic representation of the forces acting on the mandible during static biting and the resulting bone deformation patterns described in the literature. Image built using a three-dimensional reconstruction of CT-data from an individual in Toro-Ibacache et al. (36).

Figure 4

Hypothetical model of cross-communication between muscles and bones at the murine masticatory system. Here we relate in a graphic outline the main changes described in rat/mouse models subjected to a reduction (Soft Diet) or an increase (Hard Diet) in diet consistency, as well as those described after paralysis of the masseter muscle by injection of botulinum toxin type A (BoNTA). In the hypofunctional models (Soft-diet, BoNTA), an increase in interleukin-6 (IL-6) expression and release, as well as a reduction in insulin-like growth factor 1 (IGF-1) in masseter muscle could mediate the muscle atrophy and bone loss, together with the reduced mechanical stimulation. In addition, the increased levels of RANK ligand (RANKL) in mandibular condyle after BoNTA injection could mediate both the osteoclastogenesis leading to bone loss and the muscle atrophy observed. On the other hand, consumption of a hard diet evokes an increase in IGF-1 expression in mandibular osteocytes, which could act as an anabolic factor in muscle and bone, leading to increased muscle mass and bone formation described in this model. Technical information: 3D rendering of murine skull, mandible, and masseter muscles corresponds to PTA contrast-enhanced high-resolution microCT data taken at the Max Planck Institute for Evolutionary Anthropology (Leipzig, Germany). Skull and mandible segmented with Avizo 9.2 (Thermo Scientific™, USA); masseter muscles segmented with the Biomedical Segmentation App (Biomedisa) (128). 3D rendering of hard and soft tissues performed with DRAGONFLY 4.1 (Object Research Systems, Canada). Image built using data from an individual in Balanta-Melo et al. (129).