Use it or lose it to age: A review of bone and muscle communication

Abstract

Until recently, it was assumed that the only interaction between muscle and bone is mechanical, that the muscle acts as a pulley and the bone as a lever to move the organism. A relatively new concept is that muscle, especially contracted muscle, acts as a secretory organ, regulating metabolism. An even newer concept is that bone, especially the osteocytes in bone, act as endocrine cells targeting other organs such as kidney and more recently, muscle. These two new concepts logically led to the third concept: that muscle and bone communicate via soluble factors. Crosstalk occurs through muscle factors such as myostatin, irisin, and a muscle metabolite, β-aminoisobutyric acid, BAIBA, and through bone factors such as osteocalcin, transforming growth factor beta, TGFβ, Prostaglandin E2, PGE₂ and Wnts. Some of these factors have positive and some negative effects on the opposing tissue. One feature both bone and muscle have in common is that their tissues are mechanically loaded and many of their secreted factors are regulated by load. This mechanical loading, also known as exercise, has beneficial effects on many systems leading to the hypothesis that muscle and bone factors can be responsible for the beneficial effects of exercise. Many of the characteristics of aging and diseases associated with aging such as sarcopenia and osteoporosis and neurological conditions such as Alzheimer's disease and dementia, are delayed by exercise. This beneficial effect has been ascribed to increased blood flow increasing oxygen and nutrients, but could also be due to the secretome of the musculoskeletal system as outlined in this review.

Keywords: Aging; Bone; Muscle; Osteocyte.

Figure 1.

Not only mechanical, but also biochemical signaling is important for optimal functioning of the musculoskeletal system. Though the mechanical interaction between bone and muscle (the muscle acting as a pulley and the bone as a lever) has long been recognized, a new area of research focuses on molecular signaling between these two tissues. The combination of mechanical loading and positive biochemical signals are synergistic, providing more potent effects than either stimuli alone.

Figure 2.

There are both positive and negative factors secreted by muscle and bone. Contraction of muscle and loading of bone appear to induce the release of positive factors. The muscle factor myostatin not only has negative effects on muscle mass but also on bone. The factors RANKL and TGFβ, released during bone resorption, have negative effects on muscle. At this time, the effects of exercise, age, stress, and circadian rhythm on this crosstalk is unknown providing a fertile area for future investigations.