Endocrine Crosstalk Between Muscle and Bone

Abstract

The musculoskeletal system is a complex organ comprised of the skeletal bones, skeletal muscles, tendons, ligaments, cartilage, joints, and other connective tissue that physically and mechanically interact to provide animals and humans with the essential ability of locomotion. This mechanical interaction is undoubtedly essential for much of the diverse shape and forms observed in vertebrates and even in invertebrates with rudimentary musculoskeletal systems such as fish. It makes sense from a historical point of view that the mechanical theories of musculoskeletal development have had tremendous influence of our understanding of biology, because these relationships are clear and palpable. Less visible to the naked eye or even to the microscope is the biochemical interaction among the individual players of the musculoskeletal system. It was only in recent years that we have begun to appreciate that beyond this mechanical coupling of muscle and bones, these 2 tissues function at a higher level through crosstalk signaling mechanisms that are important for the function of the concomitant tissue. Our brief review attempts to present some of the key concepts of these new concepts and is outline to present muscles and bones as secretory/endocrine organs, the evidence for mutual genetic and tissue interactions, pathophysiological examples of crosstalk, and the exciting new directions for this promising field of research aimed at understanding the biochemical/molecular coupling of these 2 intimately associated tissues.

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice

“…A growing amount of data suggests that muscle and bone can signal in a paracrine and endocrine fashion through secreted factors such as myokines and osteokines (for review [35]). Myostatin is a growth factor produced primarily by muscle, secreted into the circulation, and is a candidate for bone-muscle crosstalk as it has been shown to decrease osteogenic differentiation of bone marrow-derived mesenchymal stem cells [36].…”

Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) Gene in Osteocytes Stimulates Soleus Muscle Regeneration and Increased Size and Contractile Force with Age

“…Other work 4 has shown that the relative content and half-life of this 18-kDa fragment in bone cells is increased after treatment with AEBSF, which blocks autolytic cleavage of MBTPS1. Consistent with cre recombinase-mediated deletion of Mbtps1, the 18-kDa MBTPS1 band is barely detectable in two of three Mbtps1 cKO bone extracts and noticeably reduced in a third specimen (Fig.…”

“…Osteoid osteocytes control bone mineralization by secretion of DMP1, phosphate-regulating endopeptidase homolog, X-linked (PHEX), and matrix extracellular phosphoglycoprotein (MEPE) (1), whereas mature osteocytes secrete sclerostin, an inhibitor of bone formation, and regulate phosphate homeostasis and, indirectly, bone mineralization via production of FGF23 (2). Osteocytes are the mechanosensory cells in bone and appear to regulate muscle function and myogenesis (3)(4)(5). Specifically, deletion of connexin43 in osteoblasts/osteocytes shows it is involved in postnatal bone-muscle cross-talk via an osteocalcin-mediated stimulation of muscle formation and function (5).…”

Role of satellite cells in skeletal muscle plasticity: Beyond muscle regeneration

“…Decreased muscle function caused by physical inactivity or aging is strongly correlated with decreased bone mass and morphology 36,37) . Therefore, it has been suggested that the crosstalk between muscle and bone is mediated via mechanical stimuli and cytokines 38,39) . It is also empirically known that the interactions between muscle and bone are important during the bone repair following a fracture.…”