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Muscle–bone interactions: basic and clinical aspects

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Abstract

Muscle and bone are anatomically and functionally closely connected. The traditional concept that skeletal muscles serve to load bone and transform skeletal segments into a system of levers has been further refined into the mechanostat theory, according to which striated muscle is essential for bone development and maintenance, modelling and remodelling. Besides biomechanical function, skeletal muscle and bone are endocrine organs able to secrete factors capable of modulating biological function within their microenvironment, in nearby tissues or in distant organs. The endocrine properties of muscle and bone may serve to sense and transduce biomechanical signals such as loading, unloading or exercise, or systemic hormonal stimuli into biochemical signals. Nonetheless, given the close anatomical relationship between skeletal muscle and bone, paracrine interactions particularly at the periosteal interface can be hypothesized. These mechanisms can assume particular importance during bone and muscle healing after musculoskeletal injury. Basic studies in vitro and in rodents have helped to dissect the multiple influences of skeletal muscle on bone and/or expression of inside-organ metabolism and have served to explain clinical observations linking muscle-to-bone quality. Recent evidences pinpoint that also bone tissue is able to modulate directly or indirectly skeletal muscle metabolism, thus empowering the crosstalk hypothesis to be further tested in humans in vivo.

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References

  1. D.B. Burr, A.G. Robling, C.H. Turner, Effects of biomechanical stress on bones in animals. Bone 30, 781–786 (2002)

    PubMed  Google Scholar 

  2. Y.X. Qin, H. Lam, S. Ferreri, C. Rubin, Dynamic skeletal muscle stimulation and its potential in bone adaptation. J. Musculoskelet. Neuronal Interact. 10, 12–24 (2010)

    CAS  PubMed  Google Scholar 

  3. D.J. DiGirolamo, T.L. Clemens, S. Kousteni, The skeleton as an endocrine organ. Nat. Rev. Rheumatol. 8, 674–683 (2012)

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  5. S.C. Forbes, J.P. Little, D.G. Candow, Exercise and nutritional interventions for improving aging muscle health. Endocrine 42, 29–38 (2012)

    CAS  PubMed  Google Scholar 

  6. B.K. Pedersen, Muscles and their myokines. J. Exp. Biol. 214, 337–346 (2011)

    CAS  PubMed  Google Scholar 

  7. F. Norheim, T. Raastad, B. Thiede, A.C. Rustan, C.A. Drevon, F. Haugen, Proteomic identification of secreted proteins from human skeletal muscle cells and expression in response to strength training. Am. J. Physiol. Endocrinol. Metab. 301, E1013–E1021 (2011)

    CAS  PubMed  Google Scholar 

  8. S. Bortoluzzi, P. Scannapieco, A. Cestaro, G.A. Danieli, S. Schiaffino, Computational reconstruction of the human skeletal muscle secretome. Proteins 62, 776–792 (2006)

    CAS  PubMed  Google Scholar 

  9. B.K. Pedersen, M.A. Febbraio, Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat. Rev. Endocrinol. 8, 457–465 (2012)

    CAS  PubMed  Google Scholar 

  10. M.W. Hamrick, The skeletal muscle secretome: an emerging player in muscle-bone crosstalk. BoneKEy Reports 1, Article number: 60 (2012). doi:10.1038/bonekey.2012.60

  11. E. Seeman, J.L. Hopper, N.R. Young, C. Formica, P. Goss, C. Tsalamandris, Do genetic factors explain associations between muscle strength, lean mass, and bone density? a twin study. Am. J. Physiol. 270, E320–E327 (1996)

    CAS  PubMed  Google Scholar 

  12. D. Karasik, D.P. Kiel, Evidence for pleiotropic factors in genetics of the musculoskeletal system. Bone 46, 1226–1237 (2010)

    CAS  PubMed  Google Scholar 

  13. D. Karasik, C.L. Cheung, Y. Zhou, L.A. Cupples, D.P. Kiel, S. Demissie, Genome-wide association of an integrated osteoporosis-related phenotype: is there evidence for pleiotropic genes? J. Bone Miner. Res. 27, 319–330 (2012)

    CAS  PubMed Central  PubMed  Google Scholar 

  14. C. Cooper, W. Dere, W. Evans, J.A. Kanis, R. Rizzoli, A.A. Sayer, C.C. Sieber, J.M. Kaufman, G. Abellan van Kan, S. Boonen, J. Adachi, B. Mitlak, Y. Tsouderos, Y. Rolland, J.Y. Reginster, Frailty and sarcopenia: definitions and outcome parameters. Osteoporos. Int. 23, 1839–1848 (2012)

    CAS  PubMed  Google Scholar 

  15. D. Karasik, M. Cohen-Zinder, The genetic pleiotropy of musculoskeletal aging. Front Physiol. 3, 303 (2012)

    PubMed Central  PubMed  Google Scholar 

  16. A. Tajar, I.T. Huhtaniemi, T.W. O’Neill, J.D. Finn, S.R. Pye, D.M. Lee, G. Bartfai, S. Boonen, F.F. Casanueva, G. Forti, A. Giwercman, T.S. Han, K. Kula, F. Labrie, M.E. Lean, N. Pendleton, M. Punab, D. Vanderschueren, F.C. Wu, EMAS Group, Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS). J. Clin. Endocrinol. Metab. 97, 1508–1516 (2012)

    CAS  PubMed  Google Scholar 

  17. M. Spitzer, G. Huang, S. Basaria, T.G. Travison, S. Bhasin, Risks and benefits of testosterone therapy in older men. Nat. Rev. Endocrinol. 9, 414–424 (2013)

    CAS  PubMed  Google Scholar 

  18. P. Lips, N.M. van Schoor, The effect of vitamin D on bone and osteoporosis. Best Pract. Res. Clin. Endocrinol. Metab. 25, 585–591 (2011)

    CAS  PubMed  Google Scholar 

  19. H.A. Bischoff-Ferrari, Relevance of vitamin D in muscle health. Rev. Endocr. Metab. Disord. 13, 71–77 (2012)

    CAS  PubMed  Google Scholar 

  20. L. Ceglia, S.S. Harris, Vitamin D and its role in skeletal muscle. Calcif. Tissue Int. 92, 151–162 (2013)

    CAS  PubMed  Google Scholar 

  21. C.M. Girgis, R.J. Clifton-Bligh, M.W. Hamrick, M.F. Holick, J.E. Gunton, The roles of vitamin D in skeletal muscle: form, function, and metabolism. Endocr. Rev. 34, 33–83 (2013)

    CAS  PubMed  Google Scholar 

  22. L. Schubert, H.F. DeLuca, Hypophosphatemia is responsible for skeletal muscle weakness of vitamin D deficiency. Arch. Biochem. Biophys. 500, 157–161 (2010)

    CAS  PubMed  Google Scholar 

  23. H.F. Wang, Y. DeLuca, Is the vitamin D receptor found in muscle? Endocrinology 152, 354–363 (2011)

    CAS  PubMed  Google Scholar 

  24. K.B. Hagen, H. Dagfinrud, R.H. Moe, N. Østerås, I. Kjeken, M. Grotle, G. Smedslund, Exercise therapy for bone and muscle health: an overview of systematic reviews. BMC Med. 10, 167 (2012)

    PubMed Central  PubMed  Google Scholar 

  25. A. Giustina, G. Mazziotti, E. Canalis, Growth hormone, insulin-like growth factors, and the skeleton. Endocr. Rev. 29, 535–559 (2008)

    CAS  PubMed  Google Scholar 

  26. C.G. Tahimic, Y. Wang, D.D. Bikle, Anabolic effects of IGF-1 signaling on the skeleton. Front. Endocrinol. (Lausanne) 4, 6 (2013). doi:10.3389/fendo.2013.00006. Epub 2013 Feb 4

    Google Scholar 

  27. S. Perrini, L. Laviola, M.C. Carreira, A. Cignarelli, A. Natalicchio, F. Giorgino, The GH/IGF1 axis and signalling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J. Endocrinol. 205, 201–210 (2010)

    CAS  PubMed  Google Scholar 

  28. J.K. Park, J.W. Hong, C.O. Kim, S.W. Kim, C.Y. Lim, Y.S. Chung, S.W. Kim, E.J. Lee, Sustained-release recombinant human growth hormone improves body composition and quality of life in adults with somatopause. J. Am. Geriatr. Soc. 59, 944–947 (2011)

    PubMed  Google Scholar 

  29. M.D. Mavalli, D.J. Di Girolamo, Y. Fan, R.C. Riddle, K.S. Campbell, T. van Groen, S.J. Frank, M.A. Sperling, K.A. Esser, M.M. Bamman, T.L. Clemens, Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice. J. Clin. Invest. 120, 4007–4020 (2010)

    CAS  PubMed Central  PubMed  Google Scholar 

  30. N.K. Pollock, Muscle and bone. IBMS BoneKEy 9, Article number: 25 (2012). doi:10.1038/bonekey.2012.25

  31. M.A. Bredella, P.K. Fazeli, B. Lecka-Czernik, C.J. Rosen, A. Klibanski, IGFBP-2 is a negative predictor of cold-induced brown fat and bone mineral density in young non-obese women. Bone 53, 336–339 (2013)

    CAS  PubMed  Google Scholar 

  32. J.N. Farr, N. Charkoudian, J.N. Barnes, D.G. Monroe, L.K. McCready, E.J. Atkinson, S. Amin, L.J. Melton 3rd, M.J. Joyner, S. Khosla, Relationship of sympathetic activity to bone microstructure, turnover, and plasma osteopontin levels in women. J. Clin. Endocrinol. Metab. 97, 4219–4227 (2012)

    CAS  PubMed  Google Scholar 

  33. P. Boström, J. Wu, M.P. Jedrychowski, A. Korde, L. Ye, J.C. Lo, K.A. Rasbach, E.A. Boström, J.H. Choi, J.Z. Long, S. Kajimura, M.C. Zingaretti, B.F. Vind, H. Tu, S. Cinti, K. Højlund, S.P. Gygi, B.M. Spiegelman, A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463–468 (2012)

    PubMed Central  PubMed  Google Scholar 

  34. K. Redlich, J.S. Smolen, Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat. Rev. Drug Discov 11, 234–250 (2012)

    CAS  PubMed  Google Scholar 

  35. D.J. Glass, Signaling pathways perturbing muscle mass. Curr. Opin. Clin. Nutr. Metab. Care 13, 225–229 (2010)

    CAS  PubMed  Google Scholar 

  36. W.S. Lee, W.H. Cheung, L. Qin, N. Tang, K.S. Leung, Age-associated decrease of type IIA/B human skeletal muscle fibers. Clin. Orthop. Relat. Res. 450, 231–237 (2006)

    PubMed  Google Scholar 

  37. A.J. Cruz-Jentoft, J.P. Baeyens, J.M. Bauer, Y. Boirie, T. Cederholm, F. Landi, F.C. Martin, J.P. Michel, Y. Rolland, S.M. Schneider, E. Topinková, M. Vandewoude, M. Zamboni, Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age ageing 39, 412–423 (2010)

    PubMed  Google Scholar 

  38. R.A. Fielding, B. Vellas, W.J. Evans, S. Bhasin, J.E. Morley, A.B. Newman, G. Abellan van Kan, S. Andrieu, J. Bauer, D. Breuille, T. Cederholm, J. Chandler, C. De Meynard, L. Donini, T. Harris, A. Kannt, Keime, F. Guibert, G. Onder, D. Papanicolaou, Y. Rolland, D. Rooks, C. Sieber, E. Souhami, S. Verlaan, M. Zamboni, Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J. Am. Med. Dir. Assoc. 12, 249–256 (2011)

    PubMed  Google Scholar 

  39. J.P. Gumucio, C.L. Mendias, Atrogin-1, MuRF-1, and sarcopenia. Endocrine 43, 12–21 (2013)

    CAS  PubMed Central  PubMed  Google Scholar 

  40. E. Anliker, M. Toigo, Functional assessment of the muscle-bone unit in the lower leg. J. Musculoskelet. Neuronal Interact. 12, 46–55 (2012)

    CAS  PubMed  Google Scholar 

  41. T. Montalcini, V. Migliaccio, F. Yvelise, S. Rotundo, E. Mazza, A. Liberato, A. Pujia, Reference values for handgrip strength in young people of both sexes. Endocrine 43, 342–345 (2013)

    CAS  PubMed  Google Scholar 

  42. H.H. Bolotin, A new perspective on the causal influence of soft tissue composition on DXA-measured in vivo bone mineral density. J. Bone Miner. Res. 13, 1739–1746 (1998)

    CAS  PubMed  Google Scholar 

  43. B.S. Zemel, Quantitative computed tomography and computed tomography in children. Curr. Osteoporos. Rep. 9, 284–290 (2011)

    PubMed  Google Scholar 

  44. A.M. Cheung, J.D. Adachi, D.A. Hanley, D.L. Kendler, K.S. Davison, R. Josse, J.P. Brown, L.G. Ste-Marie, R. Kremer, M.C. Erlandson, L. Dian, A.J. Burghardt, S.K. Boyd, High-Resolution peripheral quantitative computed tomography for the assessment of bone strength and structure: a review by the Canadian Bone Strength Working Group. Curr. Osteoporos. Rep. 11(2), 136–146 (2013)

    PubMed Central  PubMed  Google Scholar 

  45. E. Schoenau, C.M. Neu, B. Beck, F. Manz, F. Rauch, Bone mineral content per muscle cross-sectional area as an index of the functional muscle-bone unit. J. Bone Miner. Res. 17, 1095–1101 (2002)

    PubMed  Google Scholar 

  46. K.L. Butner, K.W. Creamer, S.M. Nickols-Richardson, S.F. Clark, W.K. Ramp, W.G. Herbert, Fat and muscle indices assessed by pQCT: relationships with physical activity and type 2 diabetes risk. J. Clin. Densitom. 15, 355–361 (2012)

    PubMed  Google Scholar 

  47. S. Coupaud, L.P. Jack, K.J. Hunt, K.J. Hunt, D.B. Allan, Muscle and bone adaptations after treadmill training in incomplete spinal cord injury: a case study using peripheral quantitative computed tomography. J. Musculoskelet. Neuronal Interact. 9, 288–297 (2009)

    CAS  PubMed  Google Scholar 

  48. N. Stolzenberg, D.L. Belavy, G. Beller, G. Armbrecht, J. Semler, D. Felsenberg, Bone strength and density via pQCT in post-menopausal osteopenic women after 9 months resistive exercise with whole body vibration or proprioceptive exercise. J. Musculoskelet. Neuronal Interact. 13, 66–76 (2013)

    CAS  PubMed  Google Scholar 

  49. A.A. Sayer, E.M. Dennison, H.E. Syddall, K. Jameson, H.J. Martin, C. Cooper, The developmental origins of sarcopenia: using peripheral quantitative computed tomography to assess muscle size in older people. J. Gerontol. A 63, 835–840 (2008)

    Google Scholar 

  50. J.N. Farr, J.L. Funk, Z. Chen, J.R. Lisse, R.M. Blew, V.R. Lee, M. Laudermilk, T.G. Lohman, S.B. Going, Skeletal muscle fat content is inversely associated with bone strength in young girls. J. Bone Miner. Res. 26, 2217–2225 (2011)

    PubMed  Google Scholar 

  51. A.K. Wong, A. Bhargava, K. Beattie, K. Beattie, C.L. Gordon, L. Pickard, C.E. Webber, A. Papaioannou, J. Adachi, J. Adachi, Muscle density, a surrogate of intermuscular adiposity derived from pQCT, is an independent correlate of fractures in women. J. Bone Miner. Res. 26(Suppl 1), 2341–2357 (2011)

    Google Scholar 

  52. T. Lang, J.A. Cauley, F. Tylavsky, D. Bauer, S. Cummings, T.B. Harris, Health ABC Study, Computed tomographic measurements of thigh muscle cross-sectional area and attenuation coefficient predict hip fracture: the health, aging, and body composition study. J. Bone Miner. Res. 25, 513–519 (2010)

    PubMed  Google Scholar 

  53. K. Deere, A. Sayers, H. Viljakainen, D. Lawlor, N. Sattar, J. Kemp, W. Fraser, J. Tobias, Distinct relationships of intramuscular and subcutaneous fat with cortical bone: findings from a cross-sectional study of young adult males and females. J. Clin. Endocrinol. Metab. 98(6), E1041 (2013)

    CAS  PubMed  Google Scholar 

  54. J.F. Baker, M. Davis, R. Alexander, B.S. Zemel, S. Mostoufi-Moab, J. Shults, M. Sulik, D.J. Schiferl, M.B. Leonard, Associations between body composition and bone density and structure in men and women across the adult age spectrum. Bone 53, 34–41 (2013)

    PubMed  Google Scholar 

  55. J.L. Ferretti, R.F. Capozza, G.R. Cointry, S.L. García, H. Plotkin, M.L. Alvarez Filgueira, J.R. Zanchetta, Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age. Bone 22, 683–690 (1998)

    CAS  PubMed  Google Scholar 

  56. H. Zhang, X. Chai, S. Li, Z. Zhang, L. Yuan, H. Xie, H. Zhou, X. Wu, Z. Sheng, E. Liao, Age-related changes in body composition and their relationship with bone mineral density decreasing rates in central south Chinese postmenopausal women. Endocrine 43, 643–650 (2013)

    CAS  PubMed  Google Scholar 

  57. N.K. Lebrasseur, S.J. Achenbach, L.J. Melton 3rd, S. Amin, S. Khosla, Skeletal muscle mass is associated with bone geometry and microstructure and serum insulin-like growth factor binding protein-2 levels in adult women and men. J. Bone Miner. Res. 27, 2159–2169 (2012)

    CAS  PubMed Central  PubMed  Google Scholar 

  58. H.M. Frost, Muscle strength, bone mass, and age-related bone loss. J. Bone Miner. Res. 12, 1547–1551 (1997)

    Google Scholar 

  59. E. Schoenau, From mechanostat theory to development of the “functional muscle-bone-unit”. J. Musculoskelet. Neuronal Interact. 5, 232–238 (2005)

    CAS  PubMed  Google Scholar 

  60. L.F. Bonewald, The amazing osteocyte. J. Bone Miner. Res. 26, 229–238 (2011)

    CAS  PubMed  Google Scholar 

  61. C. Rubin, A.S. Turner, S. Bain, C. Mallinckrodt, K. McLeod, Anabolism: low mechanical signals strengthen long bones. Nature 412, 603–604 (2001)

    CAS  PubMed  Google Scholar 

  62. F. Rauch, D.A. Bailey, A. Baxter-Jones, R. Mirwald, R. Faulkner, The ‘muscle-bone unit’ during the pubertal growth spurt. Bone 34, 771–775 (2004)

    PubMed  Google Scholar 

  63. O. Fricke, R. Beccard, O. Semler, E. Schoenau, Analyses of muscular mass and function: the impact on bone mineral density and peak muscle mass. Pediatr. Nephrol. 25, 2393–2400 (2010)

    PubMed  Google Scholar 

  64. L. Xu, Q. Wang, Q. Wang, A. Lyytikäinen, T. Mikkola, E. Völgyi, S. Cheng, P. Wiklund, E. Munukka, P. Nicholson, M. Alén, S. Cheng, Concerted actions of insulin-like growth factor 1, testosterone, and estradiol on peripubertal bone growth: a 7-year longitudinal study. J. Bone Miner. Res. 26, 2204–2211 (2011)

    CAS  PubMed  Google Scholar 

  65. G.L. Klein, L.A. Fitzpatrick, C.B. Langman, T.J. Beck, T.O. Carpenter, V. Gilsanz, I.A. Holm, M.B. Leonard, B.L. Specker, ASBMR Group, The state of pediatric bone: summary of the ASBMR pediatric bone initiative. J. Bone Miner. Res. 20, 2075–2081 (2005)

    PubMed  Google Scholar 

  66. M.B. Leonard, A. Elmi, S. Mostoufi-Moab, J. Shults, J.M. Burnham, M. Thayu, L. Kibe, R.J. Wetzsteon, B.S. Zemel, Effects of sex, race, and puberty on cortical bone and the functional muscle bone unit in children, adolescents, and young adults. J. Clin. Endocrinol. Metab. 95, 1681–1689 (2010)

    CAS  PubMed  Google Scholar 

  67. J.M. Burnham, J. Shults, H. Sembhi, B.S. Zemel, M.B. Leonard, The dysfunctional muscle-bone unit in juvenile idiopathic arthritis. J. Musculoskelet. Neuronal Interact. 6, 351–352 (2006)

    CAS  PubMed  Google Scholar 

  68. A. Tsampalieros, P. Gupta, M.R. Denburg, J. Shults, B.S. Zemel, S. Mostoufi-Moab, R.J. Wetzsteon, R.M. Herskovitz, K.M. Whitehead, M.B. Leonard, Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome. J. Bone Miner. Res. 28, 480–488 (2013)

    CAS  PubMed  Google Scholar 

  69. A. LeBlanc, R. Rowe, V. Schneider, H. Evans, T. Hedrick, Regional muscle loss after short duration spaceflight. Aviat. Space Environ. Med. 66, 1151–1154 (1995)

    CAS  PubMed  Google Scholar 

  70. T. Trappe, Influence of aging and long-term unloading on the structure and function of human skeletal muscle. Appl. Physiol. Nutr. Metab. 34, 459–464 (2009)

    CAS  PubMed Central  PubMed  Google Scholar 

  71. M.L. Bianchi, A. Mazzanti, E. Galbiati, S. Saraifoger, A. Dubini, F. Cornelio, L. Morandi, Bone mineral density and bone metabolism in Duchenne muscular dystrophy. Osteoporos. Int. 14, 761–767 (2003)

    CAS  PubMed  Google Scholar 

  72. Y. Shirazi-Fard, J.S. Kupke, S.A. Bloomfield, H.A. Hogan, Discordant recovery of bone mass and mechanical properties during prolonged recovery from disuse. Bone 52, 433–443 (2013)

    PubMed  Google Scholar 

  73. P. Szulc, S. Boutroy, S. Boutroy, N. Vilayphiou, M. Schoppet, M. Rauner, R. Chapurlat, C. Hamann, L.C. Hofbauer, Correlates of bone microarchitectural parameters and serum sclerostin levels in men: the STRAMBO study. J. Bone Miner. Res. 28(8), 1760–1770 (2013)

    CAS  PubMed  Google Scholar 

  74. P. Szulc, S. Blaizot, S. Boutroy, N. Vilayphiou, S. Boonen, R. Chapurlat, Impaired bone microarchitecture at the distal radius in older men with low muscle mass and grip strength: the STRAMBO study. J. Bone Miner. Res. 28, 169–178 (2013)

    PubMed  Google Scholar 

  75. A. Sharir, T. Stern, C. Rot, R. Shahar, E. Zelzer, Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis. Development 138, 3247–3259 (2011)

    CAS  PubMed  Google Scholar 

  76. N.C. Nowlan, J. Sharpe, K.A. Roddy, P.J. Prendergast, P. Murphy, Mechanobiology of embryonic skeletal development: insights from animal models. Birth Defects Res. C 90, 203–213 (2010)

    CAS  Google Scholar 

  77. J. Kahn, Y. Shwartz, E. Blitz, S. Krief, A. Sharir, D.A. Breitel, R. Rattenbach, F. Relaix, P. Maire, R.B. Rountree, D.M. Kingsley, E. Zelzer, Muscle contraction is necessary to maintain joint progenitor cell fate. Dev. Cell 16, 734–743 (2009)

    CAS  PubMed  Google Scholar 

  78. J.G. Hall, Analysis of Pena Shokeir phenotype. Am. J. Med. Genet. 25, 99–117 (1986)

    CAS  PubMed  Google Scholar 

  79. P. Juffer, R.T. Jaspers, P. Lips, A.D. Bakker, J. Klein-Nulend, Expression of muscle anabolic and metabolic factors in mechanically loaded MLO-Y4 osteocytes. Am. J. Physiol. Endocrinol. Metab. 302, E389–E395 (2012)

    CAS  PubMed  Google Scholar 

  80. N.C. Nowlan, C. Bourdon, G. Dumas, S. Tajbakhsh, P.J. Prendergast, P. Murphy, Developing bones are differentially affected by compromised skeletal muscle formation. Bone 46, 1275–1285 (2010)

    PubMed Central  PubMed  Google Scholar 

  81. N.C. Nowlan, G. Dumas, S. Tajbakhsh, P.J. Prendergast, P. Murphy, Biophysical stimuli induced by passive movements compensate for lack of skeletal muscle during embryonic skeletogenesis. Biomech. Model. Mechanobiol. 11, 207–219 (2012)

    PubMed  Google Scholar 

  82. S.E. Warner, D.A. Sanford, B.A. Becker, S.D. Bain, S. Srinivasan, T.S. Gross, Botox induced muscle paralysis rapidly degrades bone. Bone 38, 257–264 (2006)

    CAS  PubMed Central  PubMed  Google Scholar 

  83. D. Joulia-Ekaza, G. Cabello, The myostatin gene: physiology and pharmacological relevance. Curr. Opin. Pharmacol. 7, 310–315 (2007)

    CAS  PubMed  Google Scholar 

  84. A.C. McPherron, A.M. Lawler, S.J. Lee, Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387, 83–90 (1997)

    CAS  PubMed  Google Scholar 

  85. A.C. McPherron, S.J. Lee, Double muscling in cattle due to mutations in the myostatin gene. Proc. Natl. Acad. Sci. USA 94, 12457–12461 (1997)

    CAS  PubMed  Google Scholar 

  86. M. Schuelke, K.R. Wagner, L.E. Stolz, C. Hübner, T. Riebel, W. Kömen, T. Braun, J.F. Tobin, S.J. Lee, Myostatin mutation associated with gross muscle hypertrophy in a child. N. Engl. J. Med. 350, 2682–2688 (2004)

    CAS  PubMed  Google Scholar 

  87. T.A. Zimmers, M.V. Davies, L.G. Koniaris, P. Haynes, A.F. Esquela, K.N. Tomkinson, A.C. McPherron, N.M. Wolfman, S.J. Lee, Induction of cachexia in mice by systemically administered myostatin. Science 296, 1486–1488 (2002)

    CAS  PubMed  Google Scholar 

  88. S. Reisz-Porszasz, S. Bhasin, J.N. Artaza, R. Shen, I. Sinha-Hikim, A. Hogue, T.J. Fielder, N.F. Gonzalez-Cadavid, Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin. Am. J. Physiol. Endocrinol. Metab. 285, E876–E888 (2003)

    CAS  PubMed  Google Scholar 

  89. M.W. Hamrick, A.C. McPherron, C.O. Lovejoy, Bone mineral content and density in the humerus of myostatin-deficient mice. Calcif. Tissue Int. 71, 63–68 (2002)

    CAS  PubMed  Google Scholar 

  90. M.W. Hamrick, Increased bone mineral density in the femora of GDF8 knockout mice. Anat. Rec. 272, 388–391 (2003)

    Google Scholar 

  91. E. Montgomery, C. Pennington, M. Hamrick, Muscle-bone interactions in dystrophin-deficient and myostatin-deficient mice. Anat. Rec. 286, 814–822 (2005)

    Google Scholar 

  92. M.N. Elkasrawy, M.W. Hamrick, Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J. Musculoskelet. Neuronal Interact. 10, 56–63 (2010)

    CAS  PubMed Central  PubMed  Google Scholar 

  93. M.R. Morissette, J.C. Stricker, M.A. Rosenberg, C. Buranasombati, E.B. Levitan, M.A. Mittleman, A. Rosenzweig, Effects of myostatin deletion in aging mice. Aging Cell 8, 573–583 (2009)

    CAS  PubMed Central  PubMed  Google Scholar 

  94. M.W. Hamrick, T. Samaddar, C. Pennington, J. McCormick, Increased muscle mass with myostatin deficiency improves gains in bone strength with exercise. J. Bone Miner. Res. 21, 477–483 (2006)

    CAS  PubMed  Google Scholar 

  95. M.W. Hamrick, X. Shi, W. Zhang, C. Pennington, H. Thakore, M. Haque, B. Kang, C.M. Isales, S. Fulzele, K.H. Wenger, Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading. Bone 40, 1544–1553 (2007)

    CAS  PubMed Central  PubMed  Google Scholar 

  96. T. Guo, W. Jou, T. Chanturiya, J. Portas, O. Gavrilova, A.C. McPherron, Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. PLoS One 4, e4937 (2009)

    PubMed Central  PubMed  Google Scholar 

  97. C. Zhang, C. McFarlane, S. Lokireddy, S. Masuda, X. Ge, P.D. Gluckman, M. Sharma, R. Kambadur, Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice. Diabetologia 55, 183–193 (2012)

    CAS  PubMed  Google Scholar 

  98. M. Elkasrawy, D. Immel, X. Wen, X. Liu, L.F. Liang, M.W. Hamrick, Immunolocalization of myostatin (GDF-8) following musculoskeletal injury and the effects of exogenous myostatin on muscle and bone healing. J. Histochem. Cytochem. 60, 22–30 (2012)

    CAS  PubMed  Google Scholar 

  99. S. Lokireddy, I.W. Wijesoma, S. Bonala, M. Wei, S.K. Sze, C. McFarlane, R. Kambadur, M. Sharma, Myostatin is a novel tumoral factor that induces cancer cachexia. Biochem. J. 446, 23–36 (2012)

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Z.L. Zhang, J.W. He, Y.J. Qin, Y.Q. Hu, M. Li, H. Zhang, W.W. Hu, Y.J. Liu, J.M. Gu, Association between myostatin gene polymorphisms and peak BMD variation in Chinese nuclear families. Osteoporos. Int. 19, 39–47 (2008)

    CAS  PubMed  Google Scholar 

  101. K.M. Lakshman, S. Bhasin, C. Corcoran, L.A. Collins-Racie, L. Tchistiakova, S.B. Forlow, K. St Ledger, M.E. Burczynski, A.J. Dorner, E.R. Lavallie, Measurement of myostatin concentrations in human serum: circulating concentrations in young and older men and effects of testosterone administration. Mol. Cell. Endocrinol. 302, 26–32 (2009)

    CAS  PubMed  Google Scholar 

  102. P. Szulc, M. Schoppet, C. Goettsch, M. Rauner, T. Dschietzig, R. Chapurlat, L.C. Hofbauer, Endocrine and clinical correlates of myostatin serum concentration in men–the STRAMBO study. J. Clin. Endocrinol. Metab. 97, 3700–3708 (2012)

    CAS  PubMed  Google Scholar 

  103. M.W. Hamrick IBMS BoneKEy Reports 1, Article number: 60 (2012). doi:10.1038/bonekey.2012.60

  104. R.A. Brekken, E.H. Sage, SPARC, a matricellular protein: at the crossroads of cell-matrix communication. Matrix Biol. 19, 816–827 (2001)

    CAS  PubMed  Google Scholar 

  105. L.H. Jorgensen, S.J. Petersson, J. Sellathurai, D.C. Andersen, S. Thayssen, D.J. Sant, C.H. Jensen, H.D. Schrøder, Secreted protein acidic and rich in cysteine (SPARC) in human skeletal muscle. J. Histochem. Cytochem. 57, 29–39 (2009)

    PubMed  Google Scholar 

  106. B.R. Barnes, E.R. Szelenyi, G.L. Warren, M.L. Urso, Alterations in mRNA and protein levels of metalloproteinases-2, -9, and -14 and tissue inhibitor of metalloproteinase-2 in responses to traumatic skeletal muscle injury. Am. J. Physiol. Cell Physiol. 297, C1501–C1508 (2009)

    CAS  PubMed  Google Scholar 

  107. L.S. Quinn, B.G. Anderson, L. Strait-Bodey, A. Stroud, J. Argiles, Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. Am. J. Physiol. Endocrinol. Metab. 296, E191–E202 (2009)

    CAS  PubMed  Google Scholar 

  108. B.K. Pedersen, F. Edward, Adolph distinguished lecture: muscle as an endocrine organ: IL-6 and other myokines. J. Appl. Physiol. 107, 1006–1014 (2009)

    CAS  PubMed  Google Scholar 

  109. M.N. Weitzmann, C. Roggia, G. Toraldo, L. Weitzmann, R. Pacifici, Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. J. Clin. Invest. 110, 1643–1650 (2002)

    CAS  PubMed Central  PubMed  Google Scholar 

  110. W.M. Jackson, A.B. Aragon, J. Onodera, S.M. Koehler, Y. Ji, J.D. Bulken-Hoover, J.A. Vogler, R.S. Tuan, L.J. Nesti, Cytokine expression in muscle following traumatic injury. J. Orthop. Res. 29, 1613–1620 (2011)

    CAS  PubMed Central  PubMed  Google Scholar 

  111. K. Tanaka, E. Matsumoto, Y. Higashimaki, T. Katagiri, T. Sugimoto, S. Seino, H. Kaji, Role of osteoglycin in the linkage between muscle and bone. J. Biol. Chem. 287, 11616–11628 (2012)

    CAS  PubMed  Google Scholar 

  112. K. Tanaka, E. Matsumoto, Y. Higashimaki, T. Sugimoto, S. Seino, H. Kaji, FAM5C is a soluble osteoblast differentiation factor linking muscle to bone. Biochem. Biophys. Res. Commun. 418, 134–139 (2012)

    CAS  PubMed  Google Scholar 

  113. M.W. Hamrick, P.L. McNeil, S.L. Patterson, Role of muscle-derived growth factors in bone formation. J. Musculoskelet. Neuronal Interact. 10, 64–70 (2010)

    CAS  PubMed Central  PubMed  Google Scholar 

  114. K. Jähn, N. Lara-Castillo, L. Brotto, C.L. Mo, M.L. Johnson, M. Brotto, L.F. Bonewald, Skeletal muscle secreted factors prevent glucocorticoid-induced osteocyte apoptosis through activation of β-catenin. Eur. Cell Mater. 24, 197–209 (2012). Discussion 209–210

    PubMed Central  PubMed  Google Scholar 

  115. E.L. Abreu, M. Stern, M. Brotto, Bone-muscle interactions: ASBMR Topical Meeting, July 2012. IBMS BoneKEy 9, Article number: 239 (2012). doi:10.1038/bonekey.2012.239

  116. C. Mo, S. Romero-Suarez, L. Bonewald, M. Johnson, M. Brotto, Prostaglandin e2: from clinical applications to its potential role in bone- muscle crosstalk and myogenic differentiation. Recent Pat. Biotechnol. 6, 223–229 (2012)

    CAS  PubMed Central  PubMed  Google Scholar 

  117. G. Karsenty, Osteocalcin and the regulation of bone mass. ASBMR topical meeting on bone and skeletal muscle interaction. http://www.asbmr.org/TopicalMeeting/2012/Webcast/Session6.aspx (2012)

  118. S.I. Zacks, M.F. Sheff, Periosteal and metaplastic bone formation in mouse minced muscle regeneration. Lab. Invest. 46, 405–412 (1982)

    CAS  PubMed  Google Scholar 

  119. P.S. Landry, A. Marino, K. Sadasivan, A. Albright, Effect of soft-tissue trauma on the early periosteal response of bone to injury. J. Trauma 48, 479–483 (2000)

    CAS  PubMed  Google Scholar 

  120. S.E. Utvag, K.B. Iversen, O. Grundnes, O. Reikeras, Poor muscle coverage delays fracture healing in rats. Acta Orthop Scand. 73, 471–474 (2002)

    PubMed  Google Scholar 

  121. H. Stein, S.M. Perren, J. Cordey, J. Kenwright, R. Mosheiff, M.J. Francis, The muscle bed–a crucial factor for fracture healing: a physiological concept. Orthopedics 25, 1379–1383 (2002)

    PubMed  Google Scholar 

  122. M.M. Reverte, R. Dimitriou, N.K. Kanakaris, P.V. Giannoudis, What is the effect of compartment syndrome and fasciotomies on fracture healing in tibial fractures? Injury 42, 1402–1407 (2011)

    PubMed  Google Scholar 

  123. L.E. Harry, A. Sandison, E.M. Paleolog, U. Hansen, M.F. Pearse, J. Nanchahal, Comparison of the healing of open tibial fractures covered with either muscle or fasciocutaneous tissue in a murine model. J. Orthop. Res. 26, 1238–1244 (2008)

    PubMed  Google Scholar 

  124. S. Gopal, S. Majumder, A.G. Batchelor, S.L. Knight, S.L. Knight, P. De Boer, R.M. Smith, Fix and flap: the radical orthopaedic and plastic treatment of severe open fractures of the tibia. J. Bone Joint Surg. Br. 82, 959–966 (2000)

    CAS  PubMed  Google Scholar 

  125. A. Schindeler, R. Liu, D.G. Little, The contribution of different cell lineages to bone repair: exploring a role for muscle stem cells. Differentiation 77, 12–18 (2009)

    CAS  PubMed  Google Scholar 

  126. R. Liu, A. Schindeler, D.G. Little, The potential role of muscle in bone repair. J. Musculoskelet. Neuronal Interact. 10, 71–76 (2010)

    CAS  PubMed  Google Scholar 

  127. G.E. Glass, J.K. Chan, A. Freidin, M. Feldmann, N.J. Horwood, J. Nanchahal, TNF-alpha promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells. Proc. Natl. Acad. Sci. U S A 108, 1585–1590 (2011)

    CAS  PubMed Central  PubMed  Google Scholar 

  128. D.M. Cairns, P. Lee, T. Uchimura, C.R. Seufert, H. Kwon, L. Zeng, The role of muscle cells in regulating cartilage matrix production. J. Orthop. Res. 28, 529–536 (2010)

    CAS  PubMed Central  PubMed  Google Scholar 

  129. G. Duda, W. Taylor, T. Winkler, G. Matziolis, M. Heller, N. Haas, C. Perka, K.D. Schaser, Biomechanical, microvascular, and cellular factors promote muscle and bone re generation. Exerc. Sports Sci. Rev. 36, 64–70 (2008)

    Google Scholar 

  130. Y. Hao, Y. Ma, X. Wang, F. Jin, S. Ge, Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur. J. Orthop. Res. 30, 574–580 (2012)

    CAS  PubMed  Google Scholar 

  131. E. Kellum, H. Starr, P. Arounleut, D. Immel, S. Fulzele, K. Wenger, M.W. Hamrick, Myostatin (GDF-8) deficiency increases fracture callus size, Sox-5 expression and callus bone volume. Bone 44, 17–23 (2009)

    CAS  PubMed Central  PubMed  Google Scholar 

  132. M.W. Hamrick, P. Arounleut, E. Kellum, M. Cain, D. Immel, L.F. Liang, Recombinant myostatin (GDF-8) propeptide enhances the repair and regeneration of both muscle and bone in a model of deep penetrant musculoskeletal injury. J. Trauma 69, 579–583 (2010)

    CAS  PubMed Central  PubMed  Google Scholar 

  133. L.D. Gillespie, M.C. Robertson, W.J. Gillespie, C. Sherrington, S. Gates, L.M. Clemson, S.E. Lamb, Interventions for preventing falls in older people living in the community. Cochrane Database Syst. Rev. 9, 007146 (2012)

    Google Scholar 

  134. A. Mithal, J.P. Bonjour, S. Boonen, P. Burckhardt, H. Degens, G. El Hajj Fuleihan, R. Josse, P. Lips, J. Morales Torres, R. Rizzoli, N. Yoshimura, D.A. Wahl, C. Cooper, B. Dawson-Hughes, IOF CSA Nutrition Working Group, Impact of nutrition on muscle mass, strength, and performance in older adults. Osteoporos. Int. 24(5), 1555 (2012)

    PubMed  Google Scholar 

  135. J. Rittweger, Vibration as an exercise modality: how it may work, and what its potential might be. Eur. J. Appl. Physiol. 108, 877–904 (2010)

    PubMed  Google Scholar 

  136. J. Rittweger, G. Beller, G. Armbrecht, E. Mulder, B. Buehring, U. Gast, F. Dimeo, H. Schubert, A. de Haan, D.F. Stegeman, H. Schiessl, D. Felsenberg, Prevention of bone loss during 56 days of strict bed rest by side-alternating resistive vibration exercise. Bone 46, 137–147 (2010)

    PubMed  Google Scholar 

  137. M.E. Chan, G. Uzer, C.T. Rubin, The potential benefits and inherent risks of vibration as a non-drug therapy for the prevention and treatment of osteoporosis. Curr. Osteoporos. Rep. 11, 36–44 (2013)

    PubMed  Google Scholar 

  138. M.W. Hamrick, Myostatin (GDF-8) as a Therapeutic Target for the Prevention of Osteoporotic Fractures. IBMS BoneKEy. 7, 8–17 (2010). doi:10.1138/20100423

    Google Scholar 

  139. K. Tsuchida, M. Nakatani, K. Hitachi, A. Uezumi, Y. Sunada, H. Ageta, K. Inokuchi, Activin signaling as an emerging target for therapeutic interventions. Cell. Commun. Signal. 7, 15–19 (2009)

    PubMed Central  PubMed  Google Scholar 

  140. A.D. Mitchell, R.J. Wall, In vivo evaluation of changes in body composition of transgenic mice expressing the myostatin pro domain using dual energy X-ray absorptiometry. Growth Dev. Aging 70, 25–37 (2007)

    CAS  PubMed  Google Scholar 

  141. S.J. Lee, L.A. Reed, M.V. Davies, S. Girgenrath, M.E. Goad, K.N. Tomkinson, J.F. Wright, C. Barker, G. Ehrmantraut, J. Holmstrom, B. Trowell, B. Gertz, M.S. Jiang, S.M. Sebald, M. Matzuk, E. Li, L.F. Liang, E. Quattlebaum, R.L. Stotish, N.M. Wolfman, Regulation of muscle growth by multiple ligands signalling through activin type II receptors. Proc. Natl. Acad. Sci. U S A 102, 18117–18122 (2005)

    CAS  PubMed Central  PubMed  Google Scholar 

  142. S. Bogdanovich, T.O. Krag, E.R. Barton, L.D. Morris, L.A. Whittemore, R.S. Ahima, T.S. Khurana, Functional improvement of dystrophic muscle by myostatin blockade. Nature 420, 418–421 (2002)

    CAS  PubMed  Google Scholar 

  143. K.R. Wagner, J.L. Fleckenstein, A.A. Amato, R.J. Barohn, K. Bushby, D.M. Escolar, K.M. Flanigan, A. Pestronk, R. Tawil, G.I. Wolfe, M. Eagle, J.M. Florence, W.M. King, S. Pandya, V. Straub, P. Juneau, K. Meyers, C. Csimma, T. Araujo, R. Allen, S.A. Parsons, J.M. Wozney, E.R. Lavallie, J.R. Mendell, A phase I/II trial of MYO-029 in adult subjects with muscular dystrophy. Ann. Neurol. 63, 561–571 (2008)

    CAS  PubMed  Google Scholar 

  144. N.K. LeBrasseur, T.M. Schelhorn, B.L. Bernardo, P.G. Cosgrove, P.M. Loria, T.A. Brown, Myostatin inhibition enhances the effects of exercise on performance and metabolic outcomes in aged mice. J. Gerontol. A 64, 940–948 (2009)

    Google Scholar 

  145. P. Bialek, J. Parkington, L. Warner, M. St. Andre, L. Jian, D. Gavin, C. Wallace, J. Zhang, G. Yan, A. Root, H. Seeherman, P. Yaworsky, Mice treated with a myostatin/GDF-8 decoy receptor, ActRIIB-Fc, exhibit a tremendous increase in bone mass. Bone 42(Suppl 1), S46 (2008)

    Google Scholar 

  146. V. Ferguson, R. Paietta, L. Stodieck, A. Hanson, M. Young, T. Bateman, M. Lemus, P. Kostenuik, E. Jiao, X. Zhou, J. Lu, W. Simonet, D. Lacey, H. Han, Inhibiting myostatin prevents microgravity-associated bone loss in mice. J. Bone Miner. Res. 24(Suppl 1), 1288 (2009)

    Google Scholar 

  147. K.M. Attie, N.G. Borgstein, Y. Yang, C.H. Condon, D.M. Wilson, A.E. Pearsall, R. Kumar, D.A. Willins, J.S. Seehra, M.L. Sherman, A single ascending-dose study of muscle regulator ace-031 in healthy volunteers. Muscle Nerve 47, 416–423 (2013)

    CAS  PubMed  Google Scholar 

  148. O. Guardiola, P. Lafuste, S. Brunelli, S. Iaconis, T. Touvier, P. Mourikis, K. De Bock, E. Lonardo, G. Andolfi, A. Bouché, G.L. Liguori, M.M. Shen, S. Tajbakhsh, G. Cossu, P. Carmeliet, G. Minchiotti, Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin. Proc. Natl. Acad. Sci. U S A 109, E3231–E3240 (2012)

    CAS  PubMed Central  PubMed  Google Scholar 

  149. H. Yamamoto, E.G. Williams, L. Mouchiroud, C. Cantó, W. Fan, M. Downes, C. Héligon, G.D. Barish, B. Desvergne, R.M. Evans, K. Schoonjans, J. Auwerx, NCoR1 is a conserved physiological modulator of muscle mass and oxidative function. Cell 147, 827–839 (2011)

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

L.C. is recipient of a Grant on in vivo studies on bone and muscle crosstalk provided by the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS). This study was also supported by unrestricted Grant from F.I.R.M.O. Foundation to M.L.B.

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Cianferotti, L., Brandi, M.L. Muscle–bone interactions: basic and clinical aspects. Endocrine 45, 165–177 (2014). https://doi.org/10.1007/s12020-013-0026-8

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