Elsevier

Bone

Volume 80, November 2015, Pages 109-114
Bone

Review
Bone and muscle: Interactions beyond mechanical

https://doi.org/10.1016/j.bone.2015.02.010Get rights and content

Highlights

  • The major goal of this review article is to inform regarding muscle–bone crosstalk independent of loading.

  • The second goal is to summarize data that demonstrates the endocrine nature of skeletal muscle and bone.

  • The third goal is to address questions unanswered by the mechanical coupling theory of muscle bone crosstalk.

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 tissues along with vascular and nervous tissues. 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.

This article is part of a Special Issue entitled “Muscle Bone Interactions”.

Introduction

The topic of bone–muscle interactions has become of interest for basic, clinical, and translational scientists because of the realization of the implications of this emerging field of research [1]. The concept that bone and muscle cells communicate at the biochemical and molecular levels in ways beyond and complementary to those ways dictated by mechanical interactions is leading to new insight into how bone and muscles work together in health and disease. With life expectancy projected to surpass the centenary mark, the twin diseases osteoporosis–sarcopenia will exert additional, not yet fully understood, consequences on public health and the economy. In fact, humankind has never experienced a larger and broader demographic shift in its history with a projected 20% of the world population being 60 and older by 2050 and over 1/3 by 2150 [2], [3].

Section snippets

The mechanical coupling of bone and muscle is easier to appreciate and comprehend than biochemical cross-talk

The coupling of bones and skeletal muscles has been simplified and mainly viewed as mechanical in nature, where muscles are the load suppliers and bone simply provides the attachment sites. The musculoskeletal system is unquestionably much more complex than just bone and muscles. A broader comprehension of bone–muscle biochemical signaling could lead to unprecedented and previously unimagined therapies not only for these diseases, but likely for many other musculoskeletal diseases.

The close

Muscle as a secretory/endocrine organ

It was only during the last decade of research that skeletal muscles were recognized for their significant secretory capacity [7]. Myostatin, discovered in Se-Jin's laboratory in 1997 is arguably the most potent inhibitor of skeletal muscle cell proliferation and growth and is also considered one of the earliest muscle secreted factors [8], [9].

Pedersen and colleagues were the first research group to invent the term, ‘myokines,’ and since then, other muscle secreted factors have been documented

Bone as a secretory/endocrine organ

Bone is generally not thought of as an endocrine gland such as the pituitary or adrenals. However, the definition of an endocrine gland is that it must be highly vascularized and form a system that directly secretes hormones into the bloodstream to affect distant targets. Based on this definition, bone is an endocrine organ [15]. Osteoblasts have the capacity to release factors such as osteocalcin as do osteocytes. In addition, osteocytes produce circulating factors such as FGF23 and

Future directions

In summary, the mechanical and biochemical theories of bone–muscle crosstalk are not exclusive or one more important or relevant than the other theory. These theories are most likely complementary whereby mechanical force might prime bone and muscle for regulation and release of specific factors to exert their effects on the opposing tissue. Continued and progressive research aimed at merging these two theories will bring advances in knowledge that will translate into new therapies that could

Conflict of interest

The authors declare no conflicts of interest.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Acknowledgments

The research supported by the authors in muscle bone crosstalk is supported by NIAMS NIA PO1AG039355.

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