Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Current Osteoporosis Reports
Erschienen in: Current Osteoporosis Reports 2/2014

01.06.2014 | Muscle and Bone (L Bonewald and M Harrick, Section Editors)

Endocrine Crosstalk Between Muscle and Bone

verfasst von: Marco Brotto, Mark L. Johnson

Erschienen in: Current Osteoporosis Reports | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

The musculoskeletal system is a complex organ comprised of the skeletal bones, skeletal muscles, tendons, ligaments, cartilage, joints, and other connective tissue that physically and mechanically interact to provide animals and humans with the essential ability of locomotion. This mechanical interaction is undoubtedly essential for much of the diverse shape and forms observed in vertebrates and even in invertebrates with rudimentary musculoskeletal systems such as fish. It makes sense from a historical point of view that the mechanical theories of musculoskeletal development have had tremendous influence of our understanding of biology, because these relationships are clear and palpable. Less visible to the naked eye or even to the microscope is the biochemical interaction among the individual players of the musculoskeletal system. It was only in recent years that we have begun to appreciate that beyond this mechanical coupling of muscle and bones, these 2 tissues function at a higher level through crosstalk signaling mechanisms that are important for the function of the concomitant tissue. Our brief review attempts to present some of the key concepts of these new concepts and is outline to present muscles and bones as secretory/endocrine organs, the evidence for mutual genetic and tissue interactions, pathophysiological examples of crosstalk, and the exciting new directions for this promising field of research aimed at understanding the biochemical/molecular coupling of these 2 intimately associated tissues.
Literatur
1.
2.
Rauch F, Schoenau E. The developing bone: slave or master of its cells and molecules? Pediatr Res. 2001;50:309–14.PubMedCrossRef
3.
Land C, Schoenau E. Fetal and postnatal bone development: reviewing the role of mechanical stimuli and nutrition. Best Pract Res Clin Endocrinol Metab. 2008;22:107–18.PubMedCrossRef
4.
5.
Recker R, Lappe J, Davies K, Heaney R. Characterization of peri-menopausal bone loss: a prospective study. J Bone Miner Res. 2000;15:1965–73.PubMedCrossRef
6.
Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol. 2013;75:503–33.PubMedCentralPubMedCrossRef
7.
Kurek JB et al. The role of leukemia inhibitory factor in skeletal muscle regeneration. Muscle Nerve. 1997;20:815–22.PubMedCrossRef
8.
Allen DL et al. Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice. Am J Physiol Endocrinol Metab. 2008;294:E918–27.PubMedCrossRef
9.••
Pedersen BK. Muscle as a secretory organ. Compr Physiol. 2013;3:1337–62. The discovery of Myostatin as the first muscle secreted factor was a landmark in the fields of muscle and musculoskeletal research. This discovery opened the door for the thinking that secreted factors from muscles could have organismal effects. Also, myostatin became known as the most important negative regulator of muscle mass. PubMed
10.
Allen DL, Hittel DS, McPherron AC. Expression and function of myostatin in obesity, diabetes, and exercise adaptation. Med Sci Sports Exerc. 2011;43:1828–35.PubMedCentralPubMedCrossRef
11.
Pedersen BK et al. Searching for the exercise factor: is IL-6 a candidate. J Muscle Res Cell Motil. 2003;24:113–9.PubMedCrossRef
12.
Reihmane D, Jurka A, Tretjakos P, Dela F. Increase in IL-6, TNF-a, and MMP-9, but not sICAM-1, concentrations depends on exercise duration. Eur J Appl Physiol. 2013;113:851–88.PubMedCrossRef
13.
Libardi CA, De Souza GV, Cavaglieri CR, Madruga VA, Chacon-Mikahil MP. Effect of resistance, endurance, and concurrent training on TNF-a, IL-6, and CRP. Med Sci Sports Exerc. 2012;44:50–5.PubMedCrossRef
14.
Matthews VB et al. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia. 2009;52:1409–18.PubMedCrossRef
15.
Pedersen BK, Akerstrom TC, Nielsen AR, Fischer CP. Role of myokines in exercise and metabolism. J Appl Physiol. 2007;103(3):1093–8.
16.
Pedersen L, Olsen CH, Pedersen BK, Hojman P. Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle. Am J Physiol Endocrinol Metab. 2012;302:E831–40.PubMedCrossRef
17.
18.•
Quinn LS, Anderson BG, Strait-Bodey L, Stroud AM, Argiles JM. Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. Am J Physiol Endocrinol Metab. 2009;296:E191–202. The demonstration that the overexpression of a muscle specific myokine could alter adiposity and also increase BMD is a remarkable indication that muscle can signal to bone in a biochemical manner. PubMedCentralPubMedCrossRef
19.
Hee Park K et al. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab. 2013;98:4899–907.CrossRef
20.
Bortoluzzi S, Scannapieco P, Cestaro A, Danieli GA, Schiaffino S. Computational reconstruction of the human skeletal muscle secretome. Proteins. 2006;62:776–92.PubMedCrossRef
21.
Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8:457–65.PubMedCrossRef
22.
23.
Lee NK, Karsenty G. Reciprocal regulation of bone and energy metabolism. Trends Endocrinol Metabol. 2008;19:161–6.CrossRef
24.
DiGirolamo DJ, Clemens TL, Kousteni S. The skeleton as an endocrine organ. Nat Rev Rheumatol. 2012;8:674–83.PubMedCrossRef
25.
Guntar AR, Rosen CJ. Bone as an Endocrine Organ. Endocr Pract. 2012;18:758–62.CrossRef
26.
27.
Schwetz V, Pieber T, Obermayer-Pietsch B. Mechanisms in endocrinology: the endocrine role of the skeleton: background and clinical evidence. Eur J Endocrinol. 2012;166:959–67.PubMedCrossRef
28.
Karsenty G, Ferron M. The contribution of bone to whole-organism physiology. Nature. 2012;481:314–20.PubMedCrossRef
29.
Quarles LD. Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat Rev Endocrinol. 2012;8:276–86.PubMedCrossRef
30.
Neve A, Corrado A, Cantatore FP. Osteocytes: central conductors of bone biology in normal and pathological conditions. Acta Physiol. 2012;204:317–30.CrossRef
31.
Econs MJ et al. A PHEX Gene mutation is responsible for adult-onset Vitamin D-resistant hypophosphatemic osteomalacia: evidence that the disorder is not a distinct entity from X-Linked Hypophosphatemic Rickets. J Clin Endocrinol Metab. 1998;83:3459–62.PubMed
32.
Dallas SL, Prideaux M, Bonewald LF. The osteocyte: an endocrine cell. … and more. Endocr Rev. 2013;34:658–90.PubMedCrossRef
33.
The ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000;26:345–8.CrossRef
34.
Quarles LD. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab. 2003;285:E1–9.PubMed
35.
Liu S et al. Pathogenic role of Fgf23 in Hyp mice. Am J Physiol Endocrinol Metab. 2006;291:E38–49.PubMedCrossRef
36.
Francis F et al. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. Nat Genet. 1995;11:130–6.CrossRef
37.
Rowe PSN et al. Distribution of Mutations in the PEX Gene in Families with X-linked Hypophosphataemic Rickets (HYP). Hum Molec Genet. 1997;6:539–49.PubMedCrossRef
38.
Dixon PH et al. Mutational analysis of PHEX gene in X-Linked Hypophosphatemia. J Clin Endocrinol Metab. 1998;83:3615–23.PubMed
39.
40.
Touchberry CD et al. FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy. Am J Physiol Endocrinol Metab. 2013;304:E863–73.PubMedCentralPubMedCrossRef
41.
42.
Frost HM. Bone's Mechanostat: a 2003 update. Anat Rec. 2003;275A:1081–101.CrossRef
43.
Arden NK, Spector TD. Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. J Bone Miner Res. 1997;12:2076–81.PubMedCrossRef
44.
Silventoinen K, Magnusson PKE, Tynelius P, Kaprio J, Rasmussen F. Heritability of body size and muscle strength in young adulthood: a study of one million Swedish men. Genet Epidemiol. 2008;32:341–9.PubMedCrossRef
45.
Prior SJ et al. Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage. J Appl Physiol. 2007;103:1121–7.
46.
Costa A et al. Genetic inheritance effects on endurance and muscle strength. Sports Med. 2012;42:449–58.PubMedCrossRef
47.
Rivadeneira F et al. Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet. 2009;41:1199–206.PubMedCentralPubMedCrossRef
48.
49.
Duncan EL et al. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk. PLoS Genet. 2011;7:e1001372.PubMedCentralPubMedCrossRef
50.
Estrada K et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012;44:491–501.PubMedCentralPubMedCrossRef
51.
Lee Y, Choi S, Ji J, Song G. Pathway analysis of genome-wide association study for bone mineral density. Mol Biol Rep. 2012;39:8099–106.PubMedCrossRef
52.
Ran S et al. Bivariate genome-wide association analyses identified genes with pleiotropic effects for femoral neck bone geometry and age at menarche. PLoS One. 2013;8:e60362.PubMedCentralPubMedCrossRef
53.
54.
Zhang L, et al. Multistage genome-wide association meta-analyses identified two new loci for bone mineral density. Hum Mol Genet. 2014;23(7):1923–33. doi:10.​1093/​hmg/​ddt575.
55.
56.
Pérusse L et al. The Human gene map for performance and health-related fitness phenotypes: the 2002 Update. Med Sci Sports Exerc. 2003;35:1248–64.PubMedCrossRef
57.
Liu X-G et al. Genome-wide association and replication studies identified TRHR as an important gene for lean body mass. Am J Hum Genet. 2009;84:418–23.PubMedCentralPubMedCrossRef
58.
Thomis MA et al. Genome-wide linkage scan for resistance to muscle fatigue. Scand J Med Sci Sports. 2011;21:580–8.PubMedCrossRef
59.
Windelinckx A et al. Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene. Eur J Hum Genet. 2011;19:208–15.PubMedCentralPubMedCrossRef
60.
Hai R et al. Genome-wide association study of copy number variation identified gremlin1 as a candidate gene for lean body mass. J Hum Genet. 2012;57:33–7.PubMedCrossRef
61.
Kuo T et al. Genome-wide analysis of glucocorticoid receptor-binding sites in myotubes identifies gene networks modulating insulin signaling. Proc Natl Acad Sci. 2012;109:11160–5.PubMedCentralPubMedCrossRef
62.
Guo Y-F et al. Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study. Hum Genet. 2013;132:189–99.PubMedCentralPubMedCrossRef
63.
Cheng Y et al. Body composition and gene expression QTL mapping in mice reveals imprinting and interaction effects. BMC Genet. 2013;14:103.PubMedCrossRef
64.
Keildson S, et al. Skeletal muscle expression of phosphofructokinase is influenced by genetic variation and associated with insulin sensitivity. Diabetes. 2014;63(3):1154-65. doi:10.​2337/​db13-1301.
65.
Karasik D et al. Bivariate genome-wide linkage analysis of femoral bone traits and leg lean mass: The Framingham Study. J Bone Miner Res. 2009;24:710–8.PubMedCentralPubMedCrossRef
66.
Karasik D, Kiel DP. Evidence for pleiotropic factors in genetics of the musculoskeletal system. Bone. 2010;46:1226–37.PubMedCrossRef
67.
Gupta M et al. Identification of homogeneous genetic architecture of multiple genetically correlated traits by block clustering of genome-wide associations. J Bone Miner Res. 2011;26:1261–71.PubMedCentralPubMedCrossRef
68.
69.
Karasik D, Cohen-Zinder M. Osteoporosis genetics: year 2011 in review. Bone Key Rep. 2012;1(114):1–5.
70.
Edmondson DG, Lyons GE, Martin JF, Olson EN. Mef2 gene expression marks the cardiac and skeletal muscle lineages during mouse embryogenesis. Development. 1994;120:1251–63.PubMed
71.
Kramer I, Baertschi S, Halleux C, Keller H, Kneissel M. Mef2c deletion in osteocytes results in increased bone mass. J Bone Miner Res. 2012;27:360–73.PubMedCrossRef
72.
Grobet L et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet. 1997;17:71–4.PubMedCrossRef
73.
Kambadur R, Sharma M, Smith TPL, Bass JJ. Mutations in myostatin (GDF8) in Double-Muscled Belgian Blue and Piedmontese Cattle. Genome Res. 1997;7:910–5.PubMed
74.
75.
Clop A et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet. 2006;38:813–8.PubMedCrossRef
76.
Mosher DS et al. A mutation in the myostatin gene increases muscle mass and enhances racing performance in Heterozygote Dogs. PLoS Genet. 2007;3:e79.PubMedCentralPubMedCrossRef
77.
Zhang GX, Zhao XH, Wang JY, Ding FX, Zhang L. Effect of an exon 1 mutation in the myostatin gene on the growth traits of the Bian chicken. Anim Genet. 2012;43:458–9.PubMedCrossRef
78.
Williams M. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004;351:1030–1.PubMedCrossRef
79.
Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8:457–65.PubMedCrossRef
80.
Elkasrawy M, Hamrick M. Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact. 2010;10:56–63.PubMedCentralPubMed
81.
Williams NG et al. Endocrine actions of myostatin: systemic regulation of the IGF and IGF binding protein axis. Endocrinology. 2011;152:172–80.PubMedCentralPubMedCrossRef
82.
Perrini S et al. The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J Endocrinol. 2010;205:201–10.PubMedCrossRef
83.
Zacks SI, Sheff MF. Periosteal and metaplastic bone formation in mouse minced muscle regeneration. Lab Invest. 1982;46:405–12.PubMed
84.
Landry PS, Marino AA, Sadasivan KK, Albright JA. Effect of soft-tissue trauma on the early periosteal response of bone to injury. J Trauma. 2000;48:479–83.PubMedCrossRef
85.
Utvag SE, Iversen KB, Grundnes O, Reikeras O. Poor muscle coverage delays fracture healing in rats. Acta Orthop Scand. 2002;73:471–4.PubMedCrossRef
86.
Stein H et al. The muscle bed–a crucial factor for fracture healing: a physiological concept. Orthopedics. 2002;25:1379–83.PubMed
87.
Harry LE et al. Comparison of the healing of open tibial fractures covered with either muscle or fasciocutaneous tissue in a murine model. J Orthop Res. 2008;26:1238–44.PubMedCrossRef
88.
Gopal S, Majumder AG, Knight SL, De Boer P, Smith RM. Fix and Flap: the radical orthopedic and plastic treatment of severe open fractures of the tibia. J Bone Joint Surg (Br). 2000;82:959–66.CrossRef
89.•
Elkasrawy M et al. Immunolocalization of myostatin (GDF-8) following musculoskeletal injury and the effects of exogenous myostatin on muscle and bone healing. J Histochem Cytochem. 2012;60:22–30. This paper demonstrated that by inhibiting myostatin action early in the process of musculoskeletal injury, healing of both muscle and bone could be improved and accelerated. PubMedCentralPubMedCrossRef
90.
Schindeler A, Liu R, Little DG. The contribution of different cell lineages to bone repair: exploring a role for muscle stem cells. Differentiation. 2009;77:12–8.PubMedCrossRef
91.
Liu R, Schindeler A, Little DG. The potential role of muscle in bone repair. J Musculoskel Neuronal Interact. 2010;10:71–6.
92.
Griffin XL, Costa ML, Parsons N, Smith N. Electromagnetic field stimulation for treating delayed union or non-union of long bone fractures in adults. Cochrane Database Syst Rev, 2011;CD008471.
93.
Leon-Salas WD et al. A dual mode pulsed electro-magnetic cell stimulator produces acceleration of myogenic differentiation. Recent Pat Biotechnol. 2013;7:71–81.PubMedCentralPubMedCrossRef
94.
Fakhouri TH, Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity among older adults in the United States, 2007-2010. NCHS Data Brief. 2012;(106):1–8.
95.
Conboy IM et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433:760–4.PubMedCrossRef
96.
Jahn K et al. Skeletal muscle secreted factors prevent glucocorticoid-induced osteocyte apoptosis through activation of beta-catenin. Eur Cell Mater. 2012;24:197–209. discussion 209–110.PubMedCentralPubMed
Metadaten
Titel
Endocrine Crosstalk Between Muscle and Bone
verfasst von
Marco Brotto
Mark L. Johnson
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Current Osteoporosis Reports / Ausgabe 2/2014
Print ISSN: 1544-1873
Elektronische ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-014-0209-0

Weitere Artikel der Ausgabe 2/2014

Current Osteoporosis Reports 2/2014 Zur Ausgabe

Muscle and Bone (L Bonewald and M Harrick, Section Editors)

Therapies for Musculoskeletal Disease: Can we Treat Two Birds with One Stone?

Nutrition, Exercise, and Lifestyle in Osteoporosis (C Weaver and S Ferrari, Section Editors)

The Effects of Flavonoids on Bone

Hot Topic

Clinical Considerations of Regenerative Medicine in Osteoporosis

Biomechanics (M Silva and P Zysset, Section Editors)

Statistical Shape and Appearance Models in Osteoporosis

INVITED COMMENTARY

Bone Density Testing: Science, the Media, and Patient Care

Nutrition, Exercise, and Lifestyle in Osteoporosis (C Weaver and S Ferrari, Section Editors)

Prenatal Calcium and Vitamin D Intake, and Bone Mass in Later Life

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise