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Muscle and Bone Biology – Similarities and Differences

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Osteosarcopenia: Bone, Muscle and Fat Interactions

Abstract

Muscle and bone are similar in many ways, and factors that can stimulate anabolism or catabolism in one of these tissues may have the same effect(s) either directly or indirectly on the other tissue. Factors that may enhance the mass and strength of both tissues include pleiotropic genes such as Methyltransferase-Like Protein 21C (METTL21C) and Myocyte Enhancer Factor 2C (MEF2C), hormones such as growth hormone (GH) and Insulin like growth factor-1 (IGF-1), dietary amino acids, resident populations of mesenchymal stem cells (e.g., satellite cells and bone marrow derived stem cells [BMSCs]) and resistance exercise early in life. Shared mechanisms of tissue loss and dysfunction include fatty infiltration, cellular senescence, and molecules such as myostatin that can drive both muscle and bone loss. Important differences between these two tissues include the decoupling of muscle and bone patterning early in limb development, contrasting mechanotransduction pathways (e.g., wnt signaling in bone and p70S6K signaling in muscle), and contrasting bone geometry between males and females and between the upper and lower limb relative to lean mass. Overall the number of similarities between muscle and bone exceed the differences. Dietary protein and resistance exercise early in life can together promote the accumulation of lean mass and bone mineral, whereas novel therapies such as senolytic agents or NAD+ repletion may potentially prevent loss of muscle and bone with aging.

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Abbreviations

Akt:

Protein kinase b

Birc3:

Baculoviral IAP Repeat Containing 3

BMC:

Bone mineral content

BMD:

Bone mineral density

BMP:

Bone morphogenetic protein

BMSCs:

Bone marrow-derived mesenchymal stem cell

Ccl5:

C-C Motif Chemokine Ligand 5

CCR2:

C-C Motif Chemokine Receptor 2

COX:

Cyclo-oxygenase

CXCR4:

C-X-C Motif Chemokine Receptor 4

DAG:

Diacylglycerol

DC-STAMP:

Dendrocyte Expressed Seven Transmembrane Protein

DGK-z:

Diacylglycerol Kinase Zeta

ECM:

Extracellular matrix

FAM210A:

Family with sequence similarity 210, member A

FAP:

Fibro-adipogenic progenitor

FOXO:

Forkhead Box O

GH:

Growth hormone

Gpx:

glutathione peroxidase

GWAS:

Genome-wide association studies

Hox:

Homeobox

Hsp90:

Heat shock protein 90

IGF-1:

Insulin like growth factor

IGFBP:

nsulin like growth factor binding protein

IL:

Interleukin

IMAT:

intermuscular adipose tissue

Lmx1b:

LIM Homeobox Transcription Factor 1 Beta

Lrp:

LDL Receptor Related Protein

MAFbx:

Muscle Atrophy F-Box Protein

MEF2C:

Myocyte Enhancer Factor 2C

METTL21C:

Methyltransferase-Like Protein 21C

MHC:

Myosin heavy chain

MMP-12:

Matrix metalloproteinase-12

MRF:

Myogenic regulatory factor

MSCs:

Mesenchymal stem cell

mTOR:

Mechanistic Target Of Rapamycin Kinase

MuRF1:

Muscle-Specific RING Finger Protein 1

Myf5:

Myogenic factor 5

MyoD:

Myogenic differentiation

NAD+:

Nicotinamide adenine dinucleotide.

NFATc2:

Nuclear Factor Of Activated T Cells 2

NF-kB:

Nuclear Factor Kappa B

Nkx3:

NK3 Homeobox

NOX:

NADPH Oxidase

Ob-Rb:

Long isoform of leptin receptor

OPG:

osteoprotegerin

p70S6K/ S6K1:

Ribosomal Protein S6 Kinase B1

Pax3/7:

Paired box 3/7

PDGFR α/β:

Platelet Derived Growth Factor Receptor α/β

PGF2α:

Prostaglandin F2α

PI3K:

Phosphoinositide 3-kinase

PPAR gamma:

Peroxisome Proliferator Activated Receptor Gamma

RANKL:

Receptor Activator Of Nuclear Factor Kappa B Ligand

RUNX2:

Runt Related Transcription Factor 2

ROS:

Reactive oxygen species

SASP:

Senescence-Associated Secretory Phenotype

Sca-1:

Stem cell antigen 1

SDF-1:

Stromal Cell-Derived Factor 1

SNP:

Single nucleotide polymorphism

SOST:

Sclerostin

SOD1:

Superoxide dismutase

Sox9:

SRY box 9

SREBF1:

Sterol Regulatory Element Binding Transcription Factor 1

SSEA-4:

Stage-specific embryonic antigen 4

STRO-1:

Stromelysin-1

Tnf:

Tumor necrosis factor

Wnt:

Wingless

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Acknowledgments

Funding for this research was provided by the National Institute on Aging, US National Institutes of Health (AG 036675).

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  1. Department of Cellular Biology & Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA

    Joseph Elphingstone & Mark W. Hamrick

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  1. Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St. Albans, VIC, Australia, Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia

    Gustavo Duque

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Elphingstone, J., Hamrick, M.W. (2019). Muscle and Bone Biology – Similarities and Differences. In: Duque, G. (eds) Osteosarcopenia: Bone, Muscle and Fat Interactions. Springer, Cham. https://doi.org/10.1007/978-3-030-25890-0_1

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