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Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin

  • Muscle and Bone (L Bonewald and M Hamrick, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

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.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Yang J. Enhanced skeletal muscle for effective glucose homeostasis. Progress in molecular biology and translational science. Academic Press. 2014; p. 133–63.

  2. Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr. 2006;84:475–82.

    CAS  PubMed  Google Scholar 

  3. DiGirolamo DJ, Kiel DP, Esser KA. Bone and skeletal muscle: neighbors with closeties. J Bone Miner Res. 2013;28:1509–18.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Karsenty G, Oury F. Biology without walls: the novel endocrinology of bone. Annu Rev Physiol. 2012;74:87–105.

    Article  CAS  PubMed  Google Scholar 

  5. 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.

    Article  PubMed  Google Scholar 

  6. Bonewald LF. Osteocytes as dynamic multifunctional cells. Ann N Y Acad Sci. 2007;1116:281–90.

    Article  CAS  PubMed  Google Scholar 

  7. Bonewald LF, Johnson ML. Osteocytes, mechanosensing and Wnt signaling. Bone. 2008;42(4):606–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu R, Schindeler A, Little DG. The potential role of muscle in bone repair. J Musculoskelet Neuronal Interact. 2010;10(1):71–6.

    CAS  PubMed  Google Scholar 

  9. Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8:457–65.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Colaianni G, Grano M. Role of Irisin on the bone-muscle functional unit. Bonekey Rep. 2015;4:765.

    Article  CAS  PubMed  Google Scholar 

  13. Holmes D. Bone: Irisin boosts bone mass. Nat Rev Endocrinol. 2015;11(12):689.

    CAS  Google Scholar 

  14. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  26. 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.

    Article  CAS  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T, et al. Irisin - a myth rather than an exercise-inducible myokine. Sci Rep. 2015;5:8889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 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  Google Scholar 

  31. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

  33. 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.

    CAS  Google Scholar 

  34. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Graja A, Schulz TJ. Mechanisms of aging-related impairment of brown adipocyte development and function. Gerontology. 2015;61(3):211–7.

    Article  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by an ERISTO grant (to M.G.), a MIUR grant ex60% (to M.G.) and a SIOMMMS grant (to G.C.).

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Authors and Affiliations

  1. Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari, 70124, Bari, Italy

    G. Colaianni, T. Mongelli & S. Colucci

  2. Department of Experimental and Clinical Medicine, Center of Obesity, United Hospitals, University of Ancona, 60020, Ancona, Italy

    S. Cinti

  3. Department of Emergency and Organ Transplantation, University of Bari, Piazza Giulio Cesare 11, 70124, Bari, Italy

    Maria Grano

Authors
  1. G. Colaianni
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  2. T. Mongelli
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  3. S. Colucci
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  4. S. Cinti
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  5. Maria Grano
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Corresponding author

Correspondence to Maria Grano.

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Conflict of Interest

M. Grano, S. Cinti, Dr. Mongelli, S. Colucci and G. Colainni report grants from ERISTO, grants from MIUR ex60%, and grants from SIOMMMS, during the conduct of the study. In addition, S. Cinti, S. Colucci and G. Colainni have a patent, MI2015A000558.

Human and Animal Rights and Informed Consent

All studies by the authors involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

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This article is part of the Topical Collection on Muscle and Bone

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Colaianni, G., Mongelli, T., Colucci, S. et al. Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin. Curr Osteoporos Rep 14, 132–137 (2016). https://doi.org/10.1007/s11914-016-0313-4

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  • DOI: https://doi.org/10.1007/s11914-016-0313-4

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