The Role of Bone in Muscle Wasting.

Gordon L Klein

doi:10.3390/ijms22010392

Abstract

This review describes the role of bone resorption in muscle atrophy as well as in muscle protein anabolism. Both catabolic and anabolic pathways involve components of the proinflammatory cytokine families and release of factors stored in bone during resorption. The juxtaposition of the catabolic and anabolic resorption-dependent pathways raises new questions about control of release of factors from bone, quantity of release in a variety of conditions, and relation of factors released from bone. The catabolic responses involve release of calcium from bone into the circulation resulting in increased inflammatory response in intensity and/or duration. The release of transforming growth factor beta (TGF-β) from bone suppresses phosphorylation of the AKT/mTOR pathway and stimulates ubiquitin-mediated breakdown of muscle protein. In contrast, muscle IL-6 production is stimulated by undercarboxylated osteocalcin, which signals osteoblasts to produce more RANK ligand, stimulating resorptive release of undercarboxylated osteocalcin, which in turn stimulates muscle fiber nutrient uptake and an increase in muscle mass.

Highlights

While this review focuses on factors released by bone resorption that affect muscle wasting, it is important to mention two muscle-derived factors that may influence muscle mass possibly through interaction with bone
As we have seen with transforming growth factor (TGF)-β and osteocalcin, myostatin, though produced in muscle, stimulates osteoblastic RANKL to augment osteoclastogenesis in bone through SMAD-2-dependent nuclear factor of activated T cells, or NFATc1 [28]
Components of the inflammatory response appear to be active in the three known catabolic and anabolic effects that bone resorption products have on muscle wasting or muscle mass accretion

Summary

Introduction

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Clinical Conditions That Can Cause Resorptive Bone Loss

Factors Liberated by Bone Resorption

Bone Factor Release and Muscle Catabolism

Muscle Factors Influencing Atrophy

Discussion and Summary