The musculoskeletal system can be considered one of the most advantageous anatomo-functional outcomes that have appeared throughout the evolutionary history of the animal world. This complex system sees the interaction of several organs and tissues, mostly of the same embryogenetic derivation, which integrate different vital functions, and which go beyond the primary purpose of locomotion, into a single “organ” that develops during the period of growth, and is modelled and remodelled throughout a person’s life. At least three fundamental tissues are involved in this anatomical-functional interaction: bone tissue, striated muscle tissue and adipose tissue.
These three tissues, which have the same embryological derivation, develop from the mesodermal germ layer, which can be divided into three basic regions: paraxial, intermediate and lateral mesoderm. Somitogenesis is a fundamental step that occurs in the paraxial mesoderm where cells divide into somites. Each somite contains specific precursors for the development of the axial skeleton (sclerotome), tendons (syndetome), skeletal muscles (myotome) and the dermis (dermatome). The sclerotome develops into pre-cartilage, then into cartilage, which finally undergoes ossification. The precursors derived from the paraxial mesoderm that turn towards myogenesis are under the control of Pax3/7 (Paired Box 3/7), followed by the activation of differentiation and fusion into multinucleated syncytium, i.e. myotubes, driven by the expression of myogenic factors, such as Myf5 (Myogenic Factor 5) and MyoD (Myogenic Differentiation).
The fusion of myotubes gives rise to muscle fibres, which then group into bundles and the bundles join together to form muscle tissue. Some of these cells, so-called “satellite cells”, are Pax7+ muscle precursors that localise under the basal lamina of muscle fibres in a latent state and act as a source of myonuclei during postnatal growth and after muscle injury.
Bone and skeletal muscle tissue are intimately connected to each other from a biomechanical standpoint. Whilst bone plays a supportive role, muscle enables motor activity through the interaction of contractile proteins within sarcomeres and through their insertion through tendons onto skeletal structures. Both tissues also regulate energy metabolism through the production and release of several molecules, especially cytokines. Molecules produced by bone tissue and released into the circulation to carry out local or remote biological activity are called “osteokines”. These include Wnt, sclerostin, RANK-L (Receptor Activator of Nuclear Kappa B Ligand), osteocalcin, FGF-23 (Fibroblast Growth Factor-23), BMP (Bone Morphogenetic Protein), PGE-2 (Prostaglandin E2), and IGF-1 (Insulin like Growth Factor-1). These molecules all have one or more roles modulating muscle’s biological and functional activity. At the same time, muscle tissue produces other cytokines, known as myokines, including irisin, myostatin, various interleukins, and neurotrophic factors, which act in an autocrine, paracrine and endocrine manner. The cross-talk among the component tissues that make up the locomotor system is due precisely to the production and circulation of these different substances.
Deep knowledge of the function of the molecules involved in these complex interconnected tissue systems is necessary to identify useful therapeutic strategies for the management of musculoskeletal disorders, particularly osteosarcopenia.
There is speculation that vitamin D may be considered a “director” molecule of the inter-tissue cross-talk that governs the structural and functional efficiency of the musculoskeletal system.