Physiology of Mechanotransduction: How Do Muscle and Bone "Talk" to One Another?

Abstract

The complexity of cell interactions with their microenvironment and their ability to communicate at the autocrine, paracrine, and endocrine levels has gradually but significantly evolved in the last three decades. The musculoskeletal system has been historically recognized to be governed by a relationship of proximity and function, chiefly dictated by mechanical forces and the work of gravity itself. In this review article, we first provide a historical overview of the biomechanical theory of bone- muscle interactions. Next, we expand to detail the significant evolution in our understanding of the function of bones and muscles as secretory organs. Then, we review and discuss new evidence in support of a biochemical interaction between these two tissues. We then propose that these two models of interaction are complementary and intertwined providing for a new frontier for the investigation of how bone-muscle cross talk could be fully explored for the targeting of new therapies for musculoskeletal diseases, particularly the twin conditions of aging, osteoporosis and sarcopenia. In the last section, we explore the bone-muscle cross talk in the context of their interactions with other tissues and the global impact of these multi-tissue interactions on chronic diseases.

Keywords: Bones; Bone–muscle cross talk; Cross talk; Mechanostat; Muscles; Musculoskeletal; Myokines; Osteoporosis; Sarcopenia.

Fig. 1

Proposed model of bone–muscle cross talk. This original drawing depicts both the mechanical and biochemical aspects of the bone–muscle cross talk. The largest circle in the figure represents the organismal level with the overarching influences of genetics, nutrition, and lifestyle. The two smaller circles represent the theories discussed in the article explaining bone–muscle communication. The area of overlap signifies that neither theory operates independent of the other. The “mechanical circle” presents the established principle that increased muscle load directly contributes to increased bone mass. The dotted line suggests a similar relationship in the reverse direction. The “biochemical circle” presents the growing body of evidence related to factors that are secreted from both bones and muscles. The central area of overlap labeled increased receptor sensitivity portrays the concept that both mechanical forces and secreted factors could prime or sensitize receptors in both tissues for reciprocal activity. This central area is also influenced by the global influences of genetics, nutrition, and lifestyle. On both sides of the figure, the interconnecting levels of organization reflect the influence of systems biology on the interpretation and understanding of bone-muscle cross talk

Fig. 2

Bone–muscle cross talk, interactions with other tissues, and the impact on chronic diseases. This original drawing illustrates the concept that interactions among different tissues throughout the organism are abundant and much more complex than previously realized. In this larger context, bone–muscle cross talk remains both physiologically and pathologically relevant but is also seen as being affected by other tissues of the body. At the center of this figure is the outline of an individual, the patient. The smaller circle, closest to the patient, lists cells discussed in the text, along with factors they are known to secrete. The dashed line connecting these cells indicates that they are connected biochemically through the impact that their secreted factors have on one another. The larger circle surrounding the patient lists a number of conditions and diseases impacted by the biochemical interactions between cells listed and others. Special significance for multi-tissue/organ cross talk is revealed by pathological conditions such as obesity, diabetes, and metabolic syndrome. The dotted line of this larger circle indicates the developing understanding that these conditions and diseases impact one another. These conditions seem to directly influence sarcopenia and osteoporosis as detailed in the text