Bone and muscle: Interactions beyond mechanical

Abstract

The musculoskeletal system is significantly more complex than portrayed by traditional reductionist approaches that have focused on and studied the components of this system separately. While bone and skeletal muscle are the two largest tissues within this system, this system also includes tendons, ligaments, cartilage, joints and other connective tissue along with vascular and nervous tissue. Because the main function of this system is locomotion, the mechanical interaction among the major players of this system is essential for the many shapes and forms observed in vertebrates and even in invertebrates. Thus, it is logical that the mechanical coupling theories of musculoskeletal development exert a dominant influence on our understanding of the biology of the musculoskeletal system, because these relationships are relatively easy to observe, measure, and perturb. Certainly much less recognized is the molecular and biochemical interaction among the individual players of the musculoskeletal system. In this brief review article, we first introduce some of the key reasons why the mechanical coupling theory has dominated our view of bone-muscle interactions followed by summarizing evidence for the secretory nature of bones and muscles. Finally, a number of highly physiological questions that cannot be answered by the mechanical theories alone will be raised along with different lines of evidence that support both a genetic and a biochemical communication between bones and muscles. It is hoped that these discussions will stimulate new insights into this fertile and promising new way of defining the relationships between these closely related tissues. Understanding the cellular and molecular mechanisms responsible for biochemical communication between bone and muscle is important not only from a basic research perspective but also as a means to identify potential new therapies for bone and muscle diseases, especially for when they co-exist.

Differential Bone Loss in Mouse Models of Colon Cancer Cachexia

“…Similarly, bone regeneration and increased risk of osteoporosis have been shown in NOD/scid-IL2R${\gamma }_{\text{c}}^{\text{null}}$ animals, which exhibit defects in innate and adaptive immunity (Rapp et al, 2016), as well as in patients affected with acquired immunodeficiency syndrome (Annapoorna et al, 2004). Interestingly, the level of physical activity may also contribute to explain the loss of bone tissue across the three tumor models, especially keeping in mind that the interaction between skeletal muscle and bone tissue was initially described as mainly mechanical in nature (Brotto and Bonewald, 2015). Consistently, previous reports showed that the growth of colorectal tumors progressively affected the overall activity and physical performances in C26 hosts and Apc Min/+ mice (Baltgalvis et al, 2010; Toledo et al, 2014).…”

Perpetuating effects of androgen deficiency on insulin resistance

“…The observed correlative changes in the bone quality and lean mass are related to the proposed endocrine interactions between bone and skeletal muscle mediated through osteoclast-producing or bone marrow mesenchymal cell-producing factors that have the anabolic effects in muscle 41 . Similarly, muscle can stimulate bone development through secretion of soluble myokines 42 . The present NHP study strongly suggests that caloric restriction is not feasible for treatment of osteoporosis in ADT patients 43 , and other approaches are needed to minimize this and other muscle-related or metabolic adverse effects of ADT.…”

β-aminoisobutyric Acid, l-BAIBA, Is a Muscle-Derived Osteocyte Survival Factor

“…Bone and muscle have an intimate relationship and show synchronization of tissue mass throughout life, from development to old age (Brotto and Bonewald, 2015). Exercise maintains or increases both bone and muscle mass, whereas disuse results in a reduction in mass/function of both tissues.…”