Skip to main content
Erschienen in: Current Osteoporosis Reports 4/2016

14.06.2016 | Muscle and Bone (L Bonewald and M Hamrick, Section Editors)

Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin

verfasst von: G. Colaianni, T. Mongelli, S. Colucci, S. Cinti, Maria Grano

Erschienen in: Current Osteoporosis Reports | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Several lines of evidence have recently established that skeletal muscle is an endocrine organ producing and releasing myokines acting in a paracrine or endocrine fashion. Among these, the newly identified myokine Irisin, produced by skeletal muscle after physical exercise, was originally described as molecule able to promote energy expenditure in white adipose tissue. Recently, it has been shown that the myokine Irisin affects skeletal metabolism in vivo. Thus, mice treated with a micro-dose of r-Irisin displayed improved cortical bone mass, geometry and strength, resembling the effect of physical activity in developing an efficient load-bearing skeleton. Further studies highlighted the autocrine effect of Irisin on skeletal muscle, and research performed in humans has definitively established that Irisin is a circulating hormone-like myokine, increased by physical activity. Albeit there are still few, since Irisin has been very recently discovered, herein are summarized the most relevant research findings published on this topic.
Literatur
1.
Zurück zum Zitat Yang J. Enhanced skeletal muscle for effective glucose homeostasis. Progress in molecular biology and translational science. Academic Press. 2014; p. 133–63. Yang J. Enhanced skeletal muscle for effective glucose homeostasis. Progress in molecular biology and translational science. Academic Press. 2014; p. 133–63.
2.
Zurück zum Zitat Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr. 2006;84:475–82.PubMed Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr. 2006;84:475–82.PubMed
4.
Zurück zum Zitat Karsenty G, Oury F. Biology without walls: the novel endocrinology of bone. Annu Rev Physiol. 2012;74:87–105.CrossRefPubMed Karsenty G, Oury F. Biology without walls: the novel endocrinology of bone. Annu Rev Physiol. 2012;74:87–105.CrossRefPubMed
5.
Zurück zum Zitat Rauch F, Bailey DA, Baxter-Jones A, Mirwald R, Faulkner R. The ‘muscle–bone unit’ during the pubertal growth spurt. Bone. 2004;34:771–5.CrossRefPubMed Rauch F, Bailey DA, Baxter-Jones A, Mirwald R, Faulkner R. The ‘muscle–bone unit’ during the pubertal growth spurt. Bone. 2004;34:771–5.CrossRefPubMed
6.
Zurück zum Zitat Bonewald LF. Osteocytes as dynamic multifunctional cells. Ann N Y Acad Sci. 2007;1116:281–90.CrossRefPubMed Bonewald LF. Osteocytes as dynamic multifunctional cells. Ann N Y Acad Sci. 2007;1116:281–90.CrossRefPubMed
8.
Zurück zum Zitat Liu R, Schindeler A, Little DG. The potential role of muscle in bone repair. J Musculoskelet Neuronal Interact. 2010;10(1):71–6.PubMed Liu R, Schindeler A, Little DG. The potential role of muscle in bone repair. J Musculoskelet Neuronal Interact. 2010;10(1):71–6.PubMed
9.
Zurück zum Zitat Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8:457–65.CrossRefPubMed Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8:457–65.CrossRefPubMed
10.•
Zurück zum Zitat Colaianni G, Cuscito C, Mongelli T, Oranger A, Mori G, Brunetti G, et al. Irisin enhances osteoblast differentiation in vitro. Int J Endocrinol. 2014;2014, 902186. This is the first study showing that the myokine Irisin, produced by skeletal muscle, acts directly on osteoblasts.CrossRefPubMedPubMedCentral Colaianni G, Cuscito C, Mongelli T, Oranger A, Mori G, Brunetti G, et al. Irisin enhances osteoblast differentiation in vitro. Int J Endocrinol. 2014;2014, 902186. This is the first study showing that the myokine Irisin, produced by skeletal muscle, acts directly on osteoblasts.CrossRefPubMedPubMedCentral
11.••
Zurück zum Zitat Colaianni G, Cuscito C, Mongelli T, Pignataro P, Buccoliero C, Liu P, et al. The Myokine Irisin increases cortical bone mass. PNAS. 2015;112(39):12157–62. This study demonstrated that the treatment with low-dose of recombinant Irisin improves cortical mineral density, geometry and strength in bone of young healthy mice.CrossRefPubMedPubMedCentral Colaianni G, Cuscito C, Mongelli T, Pignataro P, Buccoliero C, Liu P, et al. The Myokine Irisin increases cortical bone mass. PNAS. 2015;112(39):12157–62. This study demonstrated that the treatment with low-dose of recombinant Irisin improves cortical mineral density, geometry and strength in bone of young healthy mice.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Colaianni G, Grano M. Role of Irisin on the bone-muscle functional unit. Bonekey Rep. 2015;4:765.CrossRefPubMed Colaianni G, Grano M. Role of Irisin on the bone-muscle functional unit. Bonekey Rep. 2015;4:765.CrossRefPubMed
13.
Zurück zum Zitat Holmes D. Bone: Irisin boosts bone mass. Nat Rev Endocrinol. 2015;11(12):689. Holmes D. Bone: Irisin boosts bone mass. Nat Rev Endocrinol. 2015;11(12):689.
14.
Zurück zum Zitat Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481:463–8.CrossRefPubMedPubMedCentral Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481:463–8.CrossRefPubMedPubMedCentral
15.••
Zurück zum Zitat Zhang Y, Li R, Meng Y, Li S, Donelan W, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 2014;63(2):514–25. This study showed that the treatment with high dose of recombinant Irisin induces the browning expansion in white adipose tissue, reducing body weight and improving glucose homeostasis.CrossRefPubMed Zhang Y, Li R, Meng Y, Li S, Donelan W, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 2014;63(2):514–25. This study showed that the treatment with high dose of recombinant Irisin induces the browning expansion in white adipose tissue, reducing body weight and improving glucose homeostasis.CrossRefPubMed
16.
Zurück zum Zitat Baxter-Jones AD, Kontulainen SA, Faulkner RA, Bailey DA. A longitudinal study of the relationship of physical activity to bone mineral accrual from adolescence to young adulthood. Bone. 2008;43(6):1101–7.CrossRefPubMed Baxter-Jones AD, Kontulainen SA, Faulkner RA, Bailey DA. A longitudinal study of the relationship of physical activity to bone mineral accrual from adolescence to young adulthood. Bone. 2008;43(6):1101–7.CrossRefPubMed
17.
Zurück zum Zitat Toma CD, Ashkar S, Gray ML, Schaffer JL, Gerstenfeld LC. Signal transduction of mechanical stimuli is dependent on microfilament integrity: identification of osteopontin as a mechanically induced gene in osteoblasts. J Bone Miner Res. 1997;12(10):1626–36.CrossRefPubMed Toma CD, Ashkar S, Gray ML, Schaffer JL, Gerstenfeld LC. Signal transduction of mechanical stimuli is dependent on microfilament integrity: identification of osteopontin as a mechanically induced gene in osteoblasts. J Bone Miner Res. 1997;12(10):1626–36.CrossRefPubMed
18.
Zurück zum Zitat Harter LV, Hruska KA, Duncan RL. Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation. Endocrinology. 1995;136(2):528–35.PubMed Harter LV, Hruska KA, Duncan RL. Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation. Endocrinology. 1995;136(2):528–35.PubMed
19.
Zurück zum Zitat Kubota T, Yamauchi M, Onozaki J, Sato S, Suzuki Y, Sodek J. Influence of an intermittent compressive force on matrix protein expression by ROS 17/2.8 cells, with selective stimulation of osteopontin. Arch Oral Biol. 1993;38(1):23–30.CrossRefPubMed Kubota T, Yamauchi M, Onozaki J, Sato S, Suzuki Y, Sodek J. Influence of an intermittent compressive force on matrix protein expression by ROS 17/2.8 cells, with selective stimulation of osteopontin. Arch Oral Biol. 1993;38(1):23–30.CrossRefPubMed
20.
Zurück zum Zitat Paszty C, Turner CH, Robinson MK. Sclerostin: a gem from the genome leads to bone-building antibodies. J Bone Miner Res. 2013;25(9):1897–904.CrossRef Paszty C, Turner CH, Robinson MK. Sclerostin: a gem from the genome leads to bone-building antibodies. J Bone Miner Res. 2013;25(9):1897–904.CrossRef
21.
Zurück zum Zitat Lin C, Jiang X, Dai Z, Guo X, Weng T, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res. 2009;24(10):1651–61.CrossRefPubMed Lin C, Jiang X, Dai Z, Guo X, Weng T, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res. 2009;24(10):1651–61.CrossRefPubMed
22.
Zurück zum Zitat Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008;23(6):860–9.CrossRefPubMed Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008;23(6):860–9.CrossRefPubMed
23.
Zurück zum Zitat Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008;283(9):5866–75.CrossRefPubMed Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008;283(9):5866–75.CrossRefPubMed
24.
Zurück zum Zitat Qiao X, Nie Y, Ma Y, Chen Y, Cheng R, Yin W, et al. Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways. Sci Rep. 2016;6:21053.CrossRefPubMedPubMedCentral Qiao X, Nie Y, Ma Y, Chen Y, Cheng R, Yin W, et al. Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways. Sci Rep. 2016;6:21053.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Singhal V, Lawson EA, Ackerman KE, Fazeli PK, Clarke H, et al. Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates. PLoS One. 2014;9(6), e100218.CrossRefPubMedPubMedCentral Singhal V, Lawson EA, Ackerman KE, Fazeli PK, Clarke H, et al. Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates. PLoS One. 2014;9(6), e100218.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Palermo A, Strollo R, Maddaloni E, Tuccinardi D, D’Onofrio L, et al. Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin Endocrinol (Oxf). 2015;82(4):615–9.CrossRef Palermo A, Strollo R, Maddaloni E, Tuccinardi D, D’Onofrio L, et al. Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin Endocrinol (Oxf). 2015;82(4):615–9.CrossRef
27.
Zurück zum Zitat Anastasilakis AD, Polyzos SA, Makras P, Gkiomisi A, Bisbinas I, et al. Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporos Int. 2014;25(5):1633–42.CrossRefPubMed Anastasilakis AD, Polyzos SA, Makras P, Gkiomisi A, Bisbinas I, et al. Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporos Int. 2014;25(5):1633–42.CrossRefPubMed
28.
Zurück zum Zitat Klangjareonchai T, Nimitphong H, Saetung S, Bhirommuang N, Samittarucksa R, et al. Circulating sclerostin and irisin are related and interact with gender to influence adiposity in adults with prediabetes. Int J Endocrinol. 2014;2014, 261545.CrossRefPubMedPubMedCentral Klangjareonchai T, Nimitphong H, Saetung S, Bhirommuang N, Samittarucksa R, et al. Circulating sclerostin and irisin are related and interact with gender to influence adiposity in adults with prediabetes. Int J Endocrinol. 2014;2014, 261545.CrossRefPubMedPubMedCentral
29.
30.••
Zurück zum Zitat Jedrychowski MP, Wrann CD, Paulo JA, Gerber KK, Szpyt J, Robinson MM, et al. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab. 2015. doi:10.1016/j.cmet.2015.08.001. This work provides evidence that human Irisin is detectable in the circulation and its synthesis is upregulated by physical activity.PubMed Jedrychowski MP, Wrann CD, Paulo JA, Gerber KK, Szpyt J, Robinson MM, et al. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab. 2015. doi:10.​1016/​j.​cmet.​2015.​08.​001. This work provides evidence that human Irisin is detectable in the circulation and its synthesis is upregulated by physical activity.PubMed
31.
Zurück zum Zitat Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, et al. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One. 2013;8(4), e60563.CrossRefPubMedPubMedCentral Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, et al. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One. 2013;8(4), e60563.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Vaughan RA, Gannon NP, Mermier CM, Conn CA. Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism. J Physiol Biochem. 2015;71(4):679–89.CrossRefPubMed Vaughan RA, Gannon NP, Mermier CM, Conn CA. Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism. J Physiol Biochem. 2015;71(4):679–89.CrossRefPubMed
33.
Zurück zum Zitat Huh JY, Dincer F, Mesfum E, Mantzoros CS. Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans. Int J Obes (Lond). 2014;38(12):1538–44. Huh JY, Dincer F, Mesfum E, Mantzoros CS. Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans. Int J Obes (Lond). 2014;38(12):1538–44.
34.••
Zurück zum Zitat Shan T, Liang X, Bi P, Kuang S. Myostatin knockout drives browning of white adipose tissue through activating the AMPK-PGC1α-Fndc5 pathway in muscle. FASEB J. 2013;27(5):1981–9. This work showed that the myokines Irisin and myostatin are inversely regulated in skeletal muscle.CrossRefPubMedPubMedCentral Shan T, Liang X, Bi P, Kuang S. Myostatin knockout drives browning of white adipose tissue through activating the AMPK-PGC1α-Fndc5 pathway in muscle. FASEB J. 2013;27(5):1981–9. This work showed that the myokines Irisin and myostatin are inversely regulated in skeletal muscle.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Elkasrawy MN, Hamrick MW. Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact. 2010;10(1):56–63.PubMedPubMedCentral Elkasrawy MN, Hamrick MW. Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact. 2010;10(1):56–63.PubMedPubMedCentral
36.
Zurück zum Zitat MacKenzie MG, Hamilton DL, Pepin M, Patton A, Baar K. Inhibition of myostatin signaling through Notch activation following acute resistance exercise. PLoS One. 2013;8(7), e68743.CrossRefPubMedPubMedCentral MacKenzie MG, Hamilton DL, Pepin M, Patton A, Baar K. Inhibition of myostatin signaling through Notch activation following acute resistance exercise. PLoS One. 2013;8(7), e68743.CrossRefPubMedPubMedCentral
37.••
Zurück zum Zitat Rahman S, Lu Y, Czernik PJ, Rosen CJ, Enerback S, Lecka-Czernik B. Inducible brown adipose tissue, or beige fat, is anabolic for the skeleton. Endocrinology. 2013;154(8):2687–701. This work demonstrated that transgenic mice overexpressing FoxC2 in adipose tissues, a murine model for BAT induction, displayed high bone mass due to increased bone formation, triggered by wingless related MMTV integration site 10b (WNT10b) and insulin-like growth factor binding protein 2 (IGFBP2), released from BAT.CrossRefPubMedPubMedCentral Rahman S, Lu Y, Czernik PJ, Rosen CJ, Enerback S, Lecka-Czernik B. Inducible brown adipose tissue, or beige fat, is anabolic for the skeleton. Endocrinology. 2013;154(8):2687–701. This work demonstrated that transgenic mice overexpressing FoxC2 in adipose tissues, a murine model for BAT induction, displayed high bone mass due to increased bone formation, triggered by wingless related MMTV integration site 10b (WNT10b) and insulin-like growth factor binding protein 2 (IGFBP2), released from BAT.CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Graja A, Schulz TJ. Mechanisms of aging-related impairment of brown adipocyte development and function. Gerontology. 2015;61(3):211–7.CrossRefPubMed Graja A, Schulz TJ. Mechanisms of aging-related impairment of brown adipocyte development and function. Gerontology. 2015;61(3):211–7.CrossRefPubMed
39.
Zurück zum Zitat Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B, et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009;23(9):3113–20.CrossRefPubMed Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B, et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009;23(9):3113–20.CrossRefPubMed
Metadaten
Titel
Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin
verfasst von
G. Colaianni
T. Mongelli
S. Colucci
S. Cinti
Maria Grano
Publikationsdatum
14.06.2016
Verlag
Springer US
Erschienen in
Current Osteoporosis Reports / Ausgabe 4/2016
Print ISSN: 1544-1873
Elektronische ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-016-0313-4

Weitere Artikel der Ausgabe 4/2016

Current Osteoporosis Reports 4/2016 Zur Ausgabe

Biomechanics (M Silva and K Jepsen, Section Editors)

Tissue-Level Mechanical Properties of Bone Contributing to Fracture Risk

Osteoporosis and Cancer (M Nanes and M Drake, Section Editors)

The Bone Microenvironment: a Fertile Soil for Tumor Growth

Rare Bone Disease (CB Langman and E Shore, Section Editors)

Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations

Arthropedia

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

Update Orthopädie und Unfallchirurgie

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