Molecular mechanisms of obesity-induced osteoporosis and muscle atrophy

Frontiers in Physiology

Volumn 7, Issue SEP, 2016, Pages

  Roy, Bipradas ^a   Curtis, Mary E ^a   Fears, Letimicia S ^a   Nahashon, Samuel N ^a   Fentress, Hugh M ^a  

^a TENNESSEE STATE UNIVERSITY   (United States)

Author keywords

5 HT; AGE; IR; Leptin; Muscle atrophy; Obesity; Osteoporosis; TNF

Indexed keywords

ANGIOTENSIN II; BIOLOGICAL MARKER; DICKKOPF 1 PROTEIN; ESTROGEN; FOLLISTATIN LIKE 1 PROTEIN; GLUCOCORTICOID; GLUCOSE; GROWTH HORMONE; INTERLEUKIN 10; INTERLEUKIN 6; LEPTIN; MITOGEN ACTIVATED PROTEIN KINASE; MYOSTATIN; OSTEOCLAST DIFFERENTIATION FACTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SOMATOMEDIN; SOMATOMEDIN C; TESTOSTERONE; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; WNT PROTEIN;

BONE STRENGTH; CELL DIFFERENTIATION; CELL KINETICS; CELL PROLIFERATION; FRACTURE; HEALING; HUMAN; LIPID METABOLISM; MICROCIRCULATION; MOLECULAR DYNAMICS; MUSCLE ATROPHY; MUSCLE CELL; NONHUMAN; OBESITY; OSSIFICATION; OSTEOBLAST; OSTEOLYSIS; OSTEOPOROSIS; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION;

EID: 84992051611     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2016.00439     Document Type: Review

References (180)

1. Abuna, R. P., Oliveira, D. F. S., Santos, D. S. T., Guerra, T. R., Rosa, A. L., and Beloti, M. M. (2016). Participation of TNF-a in inhibitory effects of adipocytes on osteoblast differentiation. J. Cell. Physiol. 231, 204-214. doi: 10.1002/jcp.25073
2. Akhmedov, D., and Berdeaux, R. (2013). The effects of obesity on skeletal muscle regeneration. Front. Physiol. 4:371. doi: 10.3389/fphys.2013.00371
3. Almeida, M., Iyer, S., Millan, M. M., Bartell, S. M., Han, L., Ambrogini, E., et al. (2013). Estrogen receptor-a signaling in osteoblast progenitors stimulates cortical bone accrual. J. Clin. Invest. 123, 394-404. doi: 10.1172/JCI65910
4. Amati, F., Dube, J. J., Alvarez-Carnero, E., Edreira, M. M., Chomentowski, P., Coen, P. M., et al. (2011). Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes 60, 2588-2597. doi: 10.2337/db10-1221
5. Andrade, D. I. S., Zemdegs, J. C., Souza, D. A. P., Watanabe, R. L., Telles, M. M., Nascimento, C. M., et al. (2015). Diet-induced obesity impairs hypothalamic glucose sensing but not glucose hypothalamic extracellular levels, as measured by microdialysis. Nutr. Diabetes 5:e162. doi: 10.1038/nutd.2015.12
6. Armamento, V. R., Sadle, C., Napoli, N., Shah, K., Chode, S., Sinacore, D. R., et al. (2012). Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training. J. Bone Miner. Res. 27, 1215-1221. doi: 10.1002/jbmr.1560
7. Arounleut, P., Bowser, M., Upadhyay, S., Shi, X. M., Fulzele, S., Johnson, M. H., et al. (2013). Absence of functional leptin receptor isoforms in the POUND (Lepr(db/lb)) mouse is associated with muscle atrophy and altered myoblast proliferation and differentiation. PLoS ONE 14:e72330. doi: 10.1371/journal.pone.0072330
8. Babenko, N. A., and Kharchenko, V. S. (2015). Modulation of insulin sensitivity of hepatocytes by the pharmacological downregulation of phospholipase D. Int. J. Endocrinol. 2015:794838. doi: 10.1155/2015/794838
9. Bala, Y., Zebaze, R., and Seeman, E. (2015). Role of cortical bone in bone fragility. Curr. Opin. Rheumatol. 27, 406-413. doi: 10.1097/BOR.0000000000000183
10. Baron, R., and Kneissel, M. (2013). WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat. Med. 19, 179-192. doi: 10.1038/nm.3074
11. Bellido, T. (2007). Osteocyte apoptosis induces bone resorption and impairs the skeletal response to weightlessness. Bonekey Osteovision 4, 252-256. doi: 10.1138/20070272
12. Bin, G., Cuifang, W., Bo, Z., Jing, W., Jin, J., Xiaoyi, T., et al. (2015). Fluid shear stress inhibits TNF-a-induced osteoblast apoptosis via ERK5 signaling pathway. Biochem. Biophys. Res. Commun. 466, 117-123. doi: 10.1016/j.bbrc.2015.08.117
13. Binkley, N. (2012). Vitamin D and osteoporosis-related fracture. Arch. Biochem. Biophys. 523, 115-122. doi: 10.1016/j.abb.2012.02.004
14. Bonaldo, P., and Sandri, M. (2013). Cellular and molecular mechanisms of muscle atrophy. Dis. Model. Mech. 6, 25-39. doi: 10.1242/dmm.010389
15. Bredella, M. A., Torriani, M., Ghomi, R. H., Thomas, B. J., Brick, D. J., Gerweck, A. V., et al. (2011). Determinants of bone mineral density in obese premenopausal women. Bone 48, 748-754. doi: 10.1016/j.bone.2010.12.011
16. Cao, J. J. (2011). Effects of obesity on bone metabolism. J. Orthop. Surg. Res. 6:30. doi: 10.1186/1749-799X-6-30
17. Carson, J. A., and Baltgalvis, K. A. (2010). Interleukin 6 as a key regulator of muscle mass during cachexia. Exerc. Sport. Sci. Rev. 38, 168-176. doi: 10.1097/JES.0b013e3181f44f11
18. Ceddia, R. B. (2005). Direct metabolic regulation in skeletal muscle and fat tissue by leptin: implications for glucose and fatty acids homeostasis. Int. J. Obes. (Lond). 29, 1175-1183. doi: 10.1038/sj.ijo.0803025
19. Chahla, S. E., Frohnert, B. I., Thomas, W., Kelly, A. S., Nathan, B. M., and Polgreen, L. E. (2015). Higher daily physical activity is associated with higher osteocalcin levels in adolescents. Prev. Med. Rep. 2, 568-571. doi: 10.1016/j.pmedr.2015.06.017
20. Chen, G., Deng, C., and Li, Y. P. (2012). TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int. J. Biol. Sci. 8, 272-288. doi: 10.7150/ijbs.2929
21. Chen, J. R., Lazarenko, O. P., Wu, X., Tong, Y., Blackburn, M. L., Shankar, K., et al. (2010). Obesity reduces bone density associated with activation of PPAR? and suppression of Wnt/β-cat in rapidly growing male rats. PLoS ONE 5:e13704. doi: 10.1371/journal.pone.0013704
22. Chen, Y. L., Chang, C. L., Sun, C. K., Wu, C. J., Tsai, T. H., Chung, S. Y., et al. (2012). Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation. J. Transl. Med. 10:86. doi: 10.1186/1479-5876-10-86
23. Cheng, H., Jiang, W., Phillips, F. M., Haydon, R. C., Peng, Y., Zhou, L., et al. (2003). Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J. Bone Joint Surg. Am. 85-A, 1544-1552.
24. Chun, T. H., Inoue, M., Morisaki, H., Yamanaka, I., Miyamoto, Y., Okamura, T., et al. (2010). Genetic link between obesity and MMP14-dependent adipogenic collagen turnover. Diabetes 59, 2484-2494. doi: 10.2337/db10-0073
25. Cipriani, C., Pepe, J., Piemonte, S., Colangelo, L., Cilli, M., and Minisola, S. (2014). Vitamin D and its relationship with obesity and muscle. Int. J. Endocrinol. 2014:841248. doi: 10.1155/2014/841248
26. Clasen, B. F., Poulsen, M. M., Escande, C., Pedersen, S. B., Moller, N., Chini, E. N., et al. (2014). Growth hormone signaling in muscle and adipose tissue of obese human subjects: associations with measuresof body composition and interaction with resveratrol treatment. J. Clin. Endocrinol. Metab. 99, E2565-E2573. doi: 10.1210/jc.2014-2215
27. Cohen, S., Nathan, J. A., and Goldberg, A. L. (2015). Muscle wasting in disease: molecular mechanisms and promising therapies. Nat. Rev. Drug. Discov. 14, 58-74. doi: 10.1038/nrd4467
28. Colomiere, M., Permezel, M., and Lappas, M. (2010). Diabetes and obesity during pregnancy alter insulin signalling and glucose transporter expression in maternal skeletal muscle and subcutaneous adipose tissue. J. Mol. Endocrinol. 44, 213-223. doi: 10.1677/JME-09-0091
29. Crane, J. D., Palanivel, R., Mottillo, E. P., Bujak, A. L., Wang, H., Ford, R. J., et al. (2015). Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Nat. Med. 21, 166-172. doi: 10.1038/nm.3766
30. Crockett, J. C., Rogers, M. J., Coxon, F. P., Hocking, L. J., and Helfrich, M. H. (2011). Bone remodeling at a glance. J. Cell Sci. 124, 991-998. doi: 10.1242/jcs.063032
31. Daffu, G., del Pozo, C. H., O'shea, K. M., Ananthakrishnan, R., Ramasamy, R., and Schmidt, A. M. (2013). Radical roles for RAGE in the pathogenesis of oxidative stress in cardiovascular diseases and beyond. Int. J. Mol. Sci. 14, 19891-19910. doi: 10.3390/ijms141019891
32. Dai, S. Q., Yu, L. P., Shi, X., Wu, H., Shao, P., Yin, G. Y., et al. (2014). Serotonin regulates osteoblast proliferation and function in vitro. Braz. J. Med Biol. Res. 47, 759-765. doi: 10.1590/1414-431X20143565
33. Dallas, S. L., Prideaux, M., and Bonewald, L. F. (2013). The osteocyte: an endocrine cell ... and more. Endocr. Rev. 34, 658-690. doi: 10.1210/er.2012-1026
34. De Larichaudy, J., Zufferli, A., Serra, F., Isidori, A. M., Naro, F., Dessalle, K., et al. (2012). TNF-a-and tumor-induced skeletal muscle atrophy involves sphingolipid metabolism. Skelet. Muscle 2:2. doi: 10.1186/2044-5040-2-2
35. Di, M. S., Cammas, A., Lian, X. J., Kovacs, E. N., Ma, J. F., Hall, D. T., et al. (2012). The translation inhibitor pateamine A prevents cachexia-induced muscle wasting in mice. Nat. Commun. 3:896. doi: 10.1038/ncomms1899
36. Djouad, F., Jackson, W. M., Bobick, B. E., Janjanin, S., Song, Y., Huang, G. T., et al. (2010). Activin A expression regulates multipotency of mesenchymal progenitor cells. Stem Cell Res. Ther. 1:11. doi: 10.1186/scrt11
37. Duan, X. Y., Xie, P. L., Ma, Y. L., and Tang, S. Y. (2011). Omentin inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells through the PI3K/Akt pathway. Amino Acids 41, 1223-1231. doi: 10.1007/s00726-010-0800-3
38. Ducy, P., and Karsenty, G. (2010). The two faces of serotonin in bone biology. J. Cell Biol. 191, 7-13. doi: 10.1083/jcb.201006123
39. Egerman, M. A., and Glass, D. J. (2014). Signaling pathways controlling skeletal muscle mass. Crit. Rev. Biochem. Mol. Biol. 49, 59-68. doi: 10.3109/10409238.2013.857291
40. Enns, D. L., and Tiidus, P. M. (2010). The influence of estrogen on skeletal muscle: sex matters. Sports Med. 40, 41-58. doi: 10.2165/11319760-000000000-00000
41. Fan, N., Sun, H., Wang, Y., Wang, Y., Zhang, L., Xia, Z., et al. (2013). Follistatin-like 1: a potential mediator of inflammation in obesity. Mediators Inflamm. 2013:752519. doi: 10.1155/2013/752519
42. Fanzani, A., Conraads, V. M., Penna, F., and Martinet, W. (2012). Molecular and cellular mechanisms of skeletal muscle atrophy: an update. J. Cachexia Sarcopenia Muscle 3, 163-179. doi: 10.1007/s13539-012-0074-6
43. Feresin, R. G., Johnson, S. A., Elam, M. L., Jo, E., Arjmandi, B. H., and Hakkak, R. (2014). Effects of obesity on bone mass and quality in ovariectomized female Zucker rats. J. Obes. 2014:690123. doi: 10.1155/2014/690123
44. Ferris, H. A., and Kahn, C. R. (2012). New mechanisms of glucocorticoid-induced insulin resistance: make no bones about it. J. Clin. Invest. 122, 3854-3857. doi: 10.1172/JCI66180
45. Freeman, E. W., Sammel, M. D., Lin, H., and Gracia, C. R. (2010). Obesity and reproductive hormone levels in the transition to menopause. Menopause 17, 718-726. doi: 10.1097/gme.0b013e3181e3a10a
46. Frost, R. A., and Lang, C. H. (2011). mTOR signaling in skeletal muscle during sepsis and inflammation: where does it all go wrong? Physiology (Bethesda). 26, 83-96. doi: 10.1152/physiol.00044.2010
47. Gallo, D., Gesmundo, I., Trovato, L., Pera, G., Gargantini, E., Minetto, M. A., et al. (2015). GH-releasing hormone promotes survival and prevents TNF-a-induced apoptosis and atrophy in C2C12 myotubes. Endocrinology 156, 3239-3252. doi: 10.1210/EN.2015-1098
48. Girgis, C. M., Clifton-Bligh, R. J., Hamrick, M. W., Holick, M. F., and Gunton, J. E. (2013). The roles of vitamin d in skeletal muscle: form, function, and metabolism. Endocr. Rev. 34, 33-83. doi: 10.1210/er.2012-1012
49. Guntur, A. R., and Rosen, C. J. (2013). IGF-1 regulation of key signaling pathways in bone. Bonekey Rep. 2:437. doi: 10.1038/bonekey.2013.171
50. Gustafson, B., Hammarstedt, A., Hedjazifar, S., Hoffmann, J. M., Svensson, P. A., Grimsby, J., et al. (2015). BMP4 and BMP antagonists regulate human white and beige adipogenesis. Diabetes 64, 1670-1681. doi: 10.2337/db14-1127
51. Gustafson, B., and Smith, U. (2012). The Wnt inhibitor dickkopf 1 and bone morphogenetic protein 4 rescue adipogenesis in hypertrophic obesity in humans. Diabetes 61, 1217-1224. doi: 10.2337/db11-1419
52. Halade, G. V., Rahman, M. M., Williams, P. J., and Fernandes, G. (2010). High fat diet-induced animal model of age-associated obesity and osteoporosis. J. Nutr. Biochem. 21, 1162-1169. doi: 10.1016/j.jnutbio.2009.10.002
53. Hall, D. T., Ma, J. F., Marco, S. D., and Gallouzi, I. E. (2011). Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia. Aging (Albany. NY). 3, 702-715. doi: 10.18632/aging.100358
54. He, J. Y., Jiang, L. S., and Dai, L. Y. (2011). The roles of the sympathetic nervous system in osteoporotic diseases: a review of experimental and clinical studies. Ageing Res. Rev. 10, 253-263. doi: 10.1016/j.arr.2011.01.002
55. Himes, C. L., and Reynolds, S. L. (2012). Effect of obesity on falls, injury, and disability. J. Am. Geriatr. Soc. 60, 124-129. doi: 10.1111/j.1532-5415.2011.03767.x
56. Hitachi, K., and Tsuchida, K. (2014). Role of microRNAs in skeletal muscle hypertrophy. Front. Physiol. 4:408. doi: 10.3389/fphys.2013.00408
57. Hittel, D. S., Berggren, J. R., Shearer, J., Boyle, K., and Houmard, J. A. (2009). Increased secretion and expression of myostatin in skeletal muscle from extremely obese women. Diabetes 58, 30-38. doi: 10.2337/db08-0943
58. Hodge, J. M., Collier, F. M., Pavlos, N. J., Kirkland, M. A., and Nicholson, G. C. (2011). M-CSF potently augments RANKL-induced resorption activation in mature human osteoclasts. PLoS ONE 6:e21462. doi: 10.1371/journal.pone.0021462
59. Hong, E. G., Ko, H. J., Cho, Y. R., Kim, H. J., Ma, Z., Yu, T. Y., et al. (2009). Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes 58, 2525-2535. doi: 10.2337/db08-1261
60. Huey, K. A., McCusker, R. H., and Kelley, K. W. (2008). Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNF-alpha, in mice lacking interleukin-10. J. Neuroimmunol. 199, 56-62. doi: 10.1016/j.jneuroim.2008.05.004
61. Im, S. S., Kwon, S. K., Kim, T. H., Kim, H. I., and Ahn, Y. H. (2007). Regulation of glucose transporter type 4 isoform gene expression in muscle and adipocytes. IUBMB Life 59, 134-145. doi: 10.1080/15216540701313788
62. 2+ and AMPK/SIRT1. Nature 464, 1313-1319. doi: 10.1038/nature08991
63. Jackuliak, P., and Payer, J. (2014). Osteoporosis, fractures, and diabetes. Int. J. Endocrinol. 2014:820615. doi: 10.1155/2014/820615
64. Jadhav, K. S., Dungan, C. M., and Williamson, D. L. (2013). Metformin limits ceramide-induced senescence in C2C12 myoblasts. Mech. Ageing Dev. 134, 548-559. doi: 10.1016/j.mad.2013.11.002
65. Jang, W. G., Jeong, B. C., Kim, E. J., Choi, H., Oh, S. H., Kim, D. K., et al. (2015). Cyclic AMP response element-binding protein H (CREBH) mediates the inhibitory actions of tumor necrosis factor a in osteoblast differentiation by stimulating SMAD1 degradation. J. Biol. Chem. 290, 13556-13566. doi: 10.1074/jbc.M114.587923
66. Jeong, J. Y., Jeoung, N. H., Park, K. G., and Lee, I. K. (2012). Transcriptional regulation of pyruvate dehydrogenase kinase. Diabetes Metab. J. 36, 328-335. doi: 10.4093/dmj.2012.36.5.328
67. Jilka, R. L., Noble, B., and Weinstein, R. S. (2013). Osteocyte apoptosis. Bone 54, 264-271. doi: 10.1016/j.bone.2012.11.038
68. Jorgensen, S. B., O'Neill, H. M., Sylow, L., Honeyman, J., Hewitt, K. A., Palanivel, R., et al. (2013). Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity. Diabetes 62, 56-64. doi: 10.2337/db12-0443
69. Kahles, F., Findeisen, H. M., and Bruemmer, D. (2014). Osteopontin: a novel regulator at the cross roads of inflammation, obesity and diabetes. Mol. Metab. 3, 384-393. doi: 10.1016/j.molmet.2014.03.004
70. Kaneshiro, S., Ebina, K., Shi, K., Higuchi, C., Hirao, M., Okamoto, M., et al. (2014). IL-6 negatively regulates osteoblast differentiation through the SHP2/MEK2 and SHP2/Akt2 pathways in vitro. J. Bone Miner. Metab. 32, 378-392. doi: 10.1007/s00774-013-0514-1
71. Karaderi, T., Drong, A. W., and Lindgren, C. M. (2015). Insights into the genetic susceptibility to type 2 diabetes from genome-wide association studies of obesity-related traits. Curr. Diab. Rep. 15, 83. doi: 10.1007/s11892-015-0648-8
72. Keramaris, N. C., Kaptanis, S., Moss, H. L., Loppini, M., Pneumaticos, S., and Maffulli, N. (2012). Endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) in bone healing. Curr. Stem Cell Res. Ther. 7, 293-301. doi: 10.2174/157488812800793081
73. Khan, I. M., Dai Perrard, X. Y., Perrard, J. L., Mansoori, A., Smith, C. W., Wu, H., et al. (2014). Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency. Atherosclerosis 233, 419-428. doi: 10.1016/j.atherosclerosis.2014.01.011
74. Kikuta, J., and Ishii, M. (2013). Osteoclast migration, differentiation and function: novel therapeutic targets for rheumatic diseases. Rheumatology (Oxford). 52, 226-234. doi: 10.1093/rheumatology/kes259
75. Kim, H. J., Higashimori, T., Park, S. Y., Choi, H., Dong, J., Kim, Y. J., et al. (2004). Differential effects of interleukin-6 and-10 on skeletal muscle and liver insulin action in vivo. Diabetes 53, 1060-1067. doi: 10.2337/diabetes.53.4.1060
76. Kim, J. H., Liu, X., Wang, J., Chen, X., Zhang, H., Kim, S. H., et al. (2013). Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther. Adv. Musculoskelet. Dis. 5, 13-31. doi: 10.1177/1759720X12466608
77. Kim, M., Bae, S., and Lim, K. M. (2013). Impact of high fat diet-induced obesity on the plasma levels of monoamine neurotransmitters in C57BL/6 mice. Biomol. Ther. (Seoul). 21, 476-480. doi: 10.4062/biomolther.2013.063
78. 2+ oscillations essential for osteoclastogenesis. J. Biol. Chem. 285, 6913-6921. doi: 10.1074/jbc.M109.051557
79. Kim, R. Y., Yang, H. J., Song, Y. M., Kim, I. S., and Hwang, S. J. (2015). Estrogen modulates bone morphogenetic protein-induced sclerostin expression through the Wnt signaling pathway. Tissue Eng. Part A 21, 2076-2088. doi: 10.1089/ten.TEA.2014.0585
80. Kode, A., Mosialou, I., Silva, B. C., Rached, M. T., Zhou, B., Wang, J., et al. (2012). FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin. J. Clin. Invest. 122, 3490-3503. doi: 10.1172/JCI64906
81. Kokabu, S., Gamer, L., Cox, K., Lowery, J., Tsuji, K., Raz, R., et al. (2012). BMP3 suppresses osteoblast differentiation of bone marrow stromal cells via interaction with Acvr2b. Mol. Endocrinol. 26, 87-94. doi: 10.1210/me.2011-1168
82. Komori, T. (2013). Functions of the osteocyte network in the regulation of bone mass. Cell Tissue Res. 352, 191-198. doi: 10.1007/s00441-012-1546-x
83. Kotsis, V., Stabouli, S., Papakatsika, S., Rizos, Z., and Parati, G. (2010). Mechanisms of obesity-induced hypertension. Hypertens. Res. 33, 386-393. doi: 10.1038/hr.2010.9
84. Kovacheva, E. L., Hikim, A. P., Shen, R., Sinha, I., and Sinha-Hikim, I. (2010). Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminalkinase, Notch, and Akt signaling pathways. Endocrinology 151, 628-638. doi: 10.1210/en.2009-1177
85. Krawczyk, S. A., Haller, J. F., Ferrante, T., Zoeller, R. A., and Corkey, B. E. (2012). Reactive oxygen species facilitate translocation of hormone sensitive lipase to the lipid droplet during lipolysis in human differentiated adipocytes. PLoS ONE 7:e34904. doi: 10.1371/journal.pone.0034904
86. Kwon, H., and Pessin, J. E. (2013). Adipokines mediate inflammation and insulin resistance. Front. Endocrinol. (Lausanne). 4:71. doi: 10.3389/fendo.2013.00071
87. Lampropoulos, C. E., Papaioannou, I., and D'Cruz, D. P. (2012). Osteoporosis-a risk factor for cardiovascular disease? Nat. Rev. Rheumatol. 8, 587-598. doi: 10.1038/nrrheum.2012.120
88. Lee, M. J., Pramyothin, P., Karastergiou, K., and Fried, S. K. (2014). Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity. Biochim. Biophys. Acta 1842, 473-481. doi: 10.1016/j.bbadis.2013.05.029
89. Lee, S. H., and Jang, H. D. (2015). Scoparone attenuates RANKL-induced osteoclastic differentiation through controlling reactive oxygen species production and scavenging. Exp. Cell Res. 331, 267-277. doi: 10.1016/j.yexcr.2014.12.018
90. Li, J., Zhang, N., Huang, X., Xu, J., Fernandes, J. C., Dai, K., et al. (2013). Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation. Cell Death Dis. 4:e832. doi: 10.1038/cddis.2013.348
91. Li, Y., Xu, S., Zhang, X., Yi, Z., and Cichello, S. (2015). Skeletal intramyocellular lipid metabolism and insulin resistance. Biophys. Rep. 1, 90-98. doi: 10.1007/s41048-015-0013-0
92. Lin, H., Wei, B., Li, G., Zheng, J., Sun, J., Chu, J., et al. (2014). Sulforaphane reverses glucocorticoid-induced apoptosis in osteoblastic cells through regulation of the Nrf2 pathway. Drug Des. Devel. Ther. 8, 973-982. doi: 10.2147/DDDT.S65410
93. Liu, Y., and Sweeney, G. (2014). Adiponectin action in skeletal muscle. Best Pract. Res. Clin. Endocrinol. Metab. 28, 33-41. doi: 10.1016/j.beem.2013.08.003
94. Lokireddy, S., Wijesoma, I. W., Sze, S. K., McFarlane, C., Kambadur, R., and Sharma, M. (2012). Identification of atrogin-1-targeted proteins during the myostatin-induced skeletal muscle wasting. Am. J. Physiol. Cell Physiol. 303, C512-C529. doi: 10.1152/ajpcell.00402.2011
95. Lotinun, S., Pearsall, R. S., Horne, W. C., and Baron, R. (2012). Activin receptor signaling: a potential therapeutic target for osteoporosis. Curr. Mol. Pharmacol. 5, 195-204. doi: 10.2174/1874467211205020195
96. MacKenzie, M. G., Hamilton, D. L., Pepin, M., Patton, A., and Baar, K. (2013). Inhibition of myostatin signaling through Notch activation following acute resistance exercise. PLoS ONE 8:e68743. doi: 10.1371/journal.pone.0068743
97. Makki, K., Froguel, P., and Wolowczuk, I. (2013). Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013:139239. doi: 10.1155/2013/139239
98. Many, A. M., and Brown, A. M. (2014). Both canonical and non-canonical Wnt signaling independently promote stem cell growth in mammospheres. PLoS ONE 9:e101800. doi: 10.1371/journal.pone.0101800
99. Martins, A. R., Nachbar, R. T., Gorjao, R., Vinolo, M. A., Festuccia, W. T., Lambertucci, R. H., et al. (2012). Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function. Lipids Health Dis. 11:30. doi: 10.1186/1476-511X-11-30
100. McAinch, A. J., Cornall, L. M., Watts, R., Hryciw, D. H., O'Brien, P. E., and Cameron-Smith, D. (2015). Increased pyruvate dehydrogenase kinase expression in cultured myotubes from obese and diabetic individuals. Eur. J. Nutr. 54, 1033-1043. doi: 10.1007/s00394-014-0780-2
101. Mitsuishi, M., Miyashita, K., Muraki, A., and Itoh, H. (2009). Angiotensin II reduces mitochondrial content in skeletal muscle and affects glycemic control. Diabetes 58, 710-717. doi: 10.2337/db08-0949
102. Moelants, E. A., Mortier, A., Van Damme, J., and Proost, P. (2013). Regulation of TNF-a with a focus on rheumatoid arthritis. Immunol. Cell Biol. 91, 393-401. doi: 10.1038/icb.2013.15
103. Moutsatsou, P., Kassi, E., and Papavassiliou, A. G. (2012). Glucocorticoid receptor signaling in bone cells. Trends. Mol. Med. 18, 348-359. doi: 10.1016/j.molmed.2012.04.005
104. Munoz-Canoves, P., Scheele, C., Pedersen, B. K., and Serrano, A. L. (2013). Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword? FEBS 280, 4131-4148. doi: 10.1111/febs.12338
105. Nassir, F., and Ibdah, J. A. (2014). Role of mitochondria in nonalcoholic fatty liver disease. Int. J. Mol. Sci. 15, 8713-8742. doi: 10.3390/ijms15058713
106. Ng, A., and Duque, G. (2010). Osteoporosis as a lipotoxic disease. IBMS BoneKEy 7, 108-123. doi: 10.1138/20100435
107. Oliveira-Junior, S. A., Martinez, P. F., Guizoni, D. M., Campos, D. H., Fernandes, T., Oliveira, E. M., et al. (2014). AT1 receptor blockade attenuates insulin resistance and myocardial remodeling in rats with diet-induced obesity. PLoS ONE 9:e86447. doi: 10.1371/journal.pone.0086447
108. O'Neill, B. T., Lauritzen, H. P., Hirshman, M. F., Smyth, G., Goodyear, L. J., and Kahn, C. R. (2015). Differential role of insulin/IGF-1 receptor signaling in muscle growth and glucose homeostasis. Cell Rep. 11, 1220-1235. doi: 10.1016/j.celrep.2015.04.037
109. Osta, B., Benedetti, G., and Miossec, P. (2014). Classical and paradoxical effects of TNF-a on bone homeostasis. Front. Immunol. 5:48. doi: 10.3389/fimmu.2014.00048
110. Oury, F., Yadav, V. K., Wang, Y., Zhou, B., Liu, X. S., Guo, X. E., et al. (2010). CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons. Genes Dev. 24, 2330-2342. doi: 10.1101/gad.1977210
111. Park, H. K., and Ahima, R. S. (2015). Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism 64, 24-34. doi: 10.1016/j.metabol.2014.08.004
112. Patel, R., Williams, D. J., and Cummins, C. L. (2014). Minireview: new molecular mediators of glucocorticoid receptor activity in metabolic tissues. Mol. Endocrinol. 28, 999-1011. doi: 10.1210/me.2014-1062
113. Paula, F. J., and Rosen, C. J. (2010). Obesity, diabetes mellitus and last but not least, osteoporosis. Arq. Bras. Endocrinol. Metab. 54, 150-157. doi: 10.1590/S0004-27302010000200010
114. Pawaputanon Na Mahasarakham, C., Ezura, Y., Kawasaki, M., Smriti, A., Moriya, S., Yamada, T., et al. (2015). BMP-2 enhances Lgr4 gene expression in osteoblastic cells. J. Cell. Physiol. 231, 887-895. doi: 10.1002/jcp.25180
115. Pellegrinelli, V., Rouault, C., Rodriguez, C. S., Albert, V., Edom-Vovard, F., Vidal-Puig, A., et al. (2015). Human adipocytes induce inflammation and atrophy in muscle cells during obesity. Diabetes 64, 3121-3134. doi: 10.2337/db15-0296
116. Pelosi, M., De Rossi, M., Barberi, L., and Musar�, A. (2014). IL-6 impairs myogenic differentiation by downmodulation of p90RSK/eEF2 and mTOR/p70S6K axes, without affecting AKT activity. BioMed Res. Int. 2014:206026. doi: 10.1155/2014/206026
117. Pereira, S. M., Costa, P. R., Assis, A. M., Santos, C. A., and Santos, D. B. (2015). Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes. Rev. 16, 341-349. doi: 10.1111/obr.12239
118. Perreault, M., and Marette, A. (2001). Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat. Med. 7, 1138-1143. doi: 10.1038/nm1001-1138
119. Pietilainen, K. H., Kaprio, J., Borg, P., Plasqui, G., Yki-J�rvinen, H., Kujala, U. M., et al. (2008). Physical inactivity and obesity: a vicious circle. Obesity (Silver Spring). 16, 409-414. doi: 10.1038/oby.2007.72
120. Polge, C., Attaix, D., and Taillandier, D. (2015). Role of E2-Ub-conjugating enzymes during skeletal muscle atrophy. Front. Physiol. 6:59. doi: 10.3389/fphys.2015.00059
121. Pramojanee, S. N., Phimphilai, M., Chattipakorn, N., and Chattipakorn, S. C. (2014). Possible roles of insulin signaling in osteoblasts. Endocr. Res. 39, 144-151. doi: 10.3109/07435800.2013.879168
122. Ramazzotti, G., Bavelloni, A., Blalock, W., Piazzi, M., Cocco, L., and Faenza, I. (2016). BMP-2 induced expression of PLCβ1 that is a positive regulator of osteoblast differentiation. J. Cell. Physiol. 231, 623-629. doi: 10.1002/jcp.25107
123. Rasi, G. S., Delalat, B., Ceto, X., Harding, F. J., Tuke, J., and Voelcker, N. H. (2016). Synergistic influence of collagen I and BMP 2 drives osteogenic differentiation of mesenchymal stem cells: a cell microarray analysis. Acta Biomater. 34, 41-52. doi: 10.1016/j.actbio.2015.07.027
124. Rauch, A., Seitz, S., Baschant, U., Schilling, A. F., Illing, A., Stride, B., et al. (2010). Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomericglucocorticoid receptor. Cell Metab. 11, 517-531. doi: 10.1016/j.cmet.2010.05.005
125. Redlich, K., and Smolen, J. S. (2012). Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat. Rev. Drug Discov. 11, 234-250. doi: 10.1038/nrd3669
126. Reinehr, T., and Roth, C. L. (2010). A new link between skeleton, obesity and insulin resistance: relationships between osteocalcin, leptin and insulin resistance in obese children before and after weight loss. Int. J. Obes. 34, 852-858. doi: 10.1038/ijo.2009.282
127. Rodriguez, A., Becerril, S., M�ndez-Gim�nez, L., Ram�rez, B., S�inz, N., Catal�n, V., et al. (2015). Leptin administration activates irisin-induced myogenesis via nitric oxide-dependent mechanisms, but reduces its effect on subcutaneous fat browning in mice. Int. J. Obes. (Lond). 39, 397-407. doi: 10.1038/ijo.2014.166
128. Rodriguez, J., Vernus, B., Chelh, I., Cassar-Malek, I., Gabillard, J. C., Hadj, S. A., et al. (2014). Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell. Mol. Life Sci. 71, 4361-4371. doi: 10.1007/s00018-014-1689-x
129. Roy, B. (2013). Biomolecular basis of the role of diabetes mellitus in osteoporosis and bone fractures. World J. Diabetes 4, 101-113. doi: 10.4239/wjd.v4.i4.101
130. Ruiz-Alcaraz, A. J., Lipina, C., Petrie, J. R., Murphy, M. J., Morris, A. D., Sutherland, C., et al. (2013). Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase. PLoS ONE 8:e56928. doi: 10.1371/journal.pone.0056928
131. Sabio, G., Kennedy, N. J., Kyros, J. C., Jung, D. Y., Ko, H. J., Ong, H., et al. (2010). Role of muscle c-Jun NH2-terminal kinase 1 in obesity-induced insulin resistance. Mol. Cell Biol. 30, 106-115. doi: 10.1128/MCB.01162-09
132. Sainz, N., Rodriguez, A., Catalan, V., Becerril, S., Ramirez, B., G�mez-Ambrosi, J., et al. (2009). Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice. PLoS ONE 4:e6808. doi: 10.1371/journal.pone.0006808
133. Sala, D., Ivanova, S., Plana, N., Ribas, V., Duran, J., Bach, D., et al. (2014). Autophagy-regulating TP53INP2 mediates muscle wasting and is repressed in diabetes. J. Clin. Invest. 124, 1914-1927. doi: 10.1172/JCI72327
134. Sanchez, D. G., Hiepen, C., Knaus, P., and Ten, D. P. (2015). Bone morphogenetic protein signaling in bone homeostasis. Bone 80, 43-59. doi: 10.1016/j.bone.2015.05.025
135. Sato, A. Y., Tu, X., McAndrews, K. A., Plotkin, L. I., and Bellido, T. (2014). Prevention of glucocorticoid induced-apoptosis of osteoblasts and osteocytes by protecting against endoplasmic reticulum (ER) stress in vitro and in vivo in female mice. Bone 73, 60-68. doi: 10.1016/j.bone.2014.12.012
136. Sawant, A., Chanda, D., Isayeva, T., Tsuladze, G., Garvey, W. T., and Ponnazhagan, S. (2012). Noggin is novel inducer of mesenchymal stem cell adipogenesis: implications for bone health and obesity. J. Biol. Chem. 287, 12241-12249. doi: 10.1074/jbc.M111.293613
137. Schakman, O., Kalista, S., Barbe, C., Loumaye, A., and Thissen, J. P. (2013). Glucocorticoid-induced skeletal muscle atrophy. Int. J. Biochem. Cell. Biol. 45, 2163-2172. doi: 10.1016/j.biocel.2013.05.036
138. Schiaffino, S., Dyar, K. A., Ciciliot, S., Blaauw, B., and Sandri, M. (2013). Mechanisms regulating skeletal muscle growth and atrophy. FEBS J. 280, 4294-4314. doi: 10.1111/febs.12253
139. Schiaffino, S., and Mammucari, C. (2011). Regulation of skeletal muscle growth by the IGF-1-Akt/PKB pathway: insights from genetic models. Skelet. Muscle 1, 14. doi: 10.1186/2044-5040-1-4
140. Segula, D. (2014). Complications of obesity in adults: a short review of the literature. Malawi Med. J. 26, 20-24.
141. Sharples, A. P., Hughes, D. C., Deane, C. S., Saini, A., Selman, C., and Stewart, C. E. (2015). Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake. Aging Cell 14, 511-523. doi: 10.1111/acel.12342
142. Sheng, Z., Tong, D., Ou, Y., Zhang, H., Zhang, Z., Li, S., et al. (2012). Serum sclerostin levels were positively correlated with fat mass and bone mineral density in central south Chinese postmenopausal women. Clin. Endocrinol. (Oxf). 76, 797-801. doi: 10.1111/j.1365-2265.2011.04315.x
143. Shimizu, N., Yoshikawa, N., Ito, N., Maruyama, T., Suzuki, Y., Takeda, S., et al. (2011). Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle. Cell Metab. 13, 170-182. doi: 10.1016/j.cmet.2011.01.001
144. Sinacore, D. R., Hastings, M. K., Bohnert, K. L., Fielder, F. A., Villareal, D., Blair, V. P. III, et al. (2008). Inflammatory osteolysis in diabetic neuropathic (charcot) arthropathies of the foot. Phys. Ther. 88, 1399-1407. doi: 10.2522/ptj.20080025
145. Sindhu, S., Thomas, R., Shihab, P., Sriraman, D., Behbehani, K., and Ahmad, R. (2015). Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation. PLoS ONE 10:e0133494. doi: 10.1371/journal.pone.0133494
146. Sishi, B., Loos, B., Ellis, B., Smith, W., du Toit, E. F., and Engelbrecht, A. M. (2011). Diet induced obesity alters signaling pathways and induces atrophy and apoptosis in skeletal muscle in a pre-diabetic rat model. Exp. Physiol. 96, 179-193. doi: 10.1113/expphysiol.2010.054189
147. Smietana, M. J., Arruda, E. M., Faulkner, J. A., Brooks, S. V., and Larkin, L. M. (2010). Reactive oxygen species on bone mineral density and mechanics in Cu, Zn superoxide dismutase (Sod1) knockout mice. Biochem. Biophys. Res. Commun. 403, 149-153. doi: 10.1016/j.bbrc.2010.11.006
148. Srinivasan, S., Koenigstein, A., Joseph, J., Sun, L., Kalyanaraman, B., Zaidi, M., et al. (2010). Role of mitochondrial reactive oxygen species in osteoclast differentiation. Ann. N. Y. Acad. Sci. 1192, 245-252. doi: 10.1111/j.1749-6632.2009.05377.x
149. Steinberg, G. R., Michell, B. J., van Denderen, B. J., Watt, M. J., Carey, A. L., Fam, B. C., et al. (2006). Tumor necrosis factor alpha-induced skeletal muscle insulin resistance involves suppression of AMP-kinase signaling. Cell Metab. 4, 465-474. doi: 10.1016/j.cmet.2006.11.005
150. Stojanovic, O. I., Lazovic, M., Lazovic, M., and Vuceljic, M. (2011). Association between atherosclerosis and osteoporosis, the role of vitamin D. Arch. Med. Sci. 7, 179-188. doi: 10.5114/aoms.2011.22066
151. Sun, S., Liu, Z., Zhou, H., Li, G., Liu, M., Yao, J., et al. (2014). The role of fucosylation in the promotion of endothelial progenitor cells in neovascularization and bone repair. Biomaterials 35, 3777-3785. doi: 10.1016/j.biomaterials.2014.01.025
152. Tahimic, C. G., Wang, Y., and Bikle, D. D. (2013). Anabolic effects of IGF-1 signaling on the skeleton. Front. Endocrinol. (Lausanne). 4:6. doi: 10.3389/fendo.2013.00006
153. Tavares, A. B., Micmacher, E., Biesek, S., Assump��o, R., Redorat, R., Veloso, U., et al. (2013). Effects of growth hormone administration on muscle strength in men over 50 years old. Int. J. Endocrinol. 2013:942030. doi: 10.1155/2013/942030
154. Thomsen, S. B., Rathcke, C. N., Zerahn, B., and Vestergaard, H. (2010). Increased levels of the calcification marker matrix Gla Protein and the inflammatory markers YKL-40 and CRP in patients with type 2 diabetes and ischemic heart disease. Cardiovasc. Diabetol. 9:86. doi: 10.1186/1475-2840-9-86
155. Tornero, E. P., Peralta, S. A., Herranz, E., Rodriguez, R. L., Mucientes, A., Abasolo, L., et al. (2015). Altered expression of Wnt signaling pathway components in osteogenesis of mesenchymal stem cells in osteoarthritis patients. PLoS ONE 10:e0137170. doi: 10.1371/journal.pone.0137170
156. Townsend, K. L., Lorenzi, M. M., and Widmaier, E. P. (2008). High-fat diet-induced changes in body mass and hypothalamic gene expression in wild-type and leptin-deficient mice. Endocrine 33, 176-188. doi: 10.1007/s12020-008-9070-1
157. Unoki, K. H., Yamagishi, S., Takeuchi, M., Bujo, H., and Saito, Y. (2010). Pyridoxamine, an inhibitor of advanced glycation end product (AGE) formation ameliorates insulin resistance in obese, type 2 diabetic mice. Protein Pept. Lett. 17, 1177-1181. doi: 10.2174/092986610791760423
158. Valerio, G., Galle, F., Mancusi, C., Di, O. V., Guida, P., Tramontano, A., et al. (2012). Prevalence of overweight in children with bone fractures: a case control study. BMC Pediatrics 12:166. doi: 10.1186/1471-2431-12-166
159. Valina, T. A. L., Lai, Z., Zhang, S., and Flack, J. M. (2012). Vitamin D and parathyroid hormone relationships with urinary nitric oxide metabolites and plasma isoprostanes in African-Americans. Cardiorenal Med. 2, 234-242. doi: 10.1159/000339942
160. Van, S. T. T., Savelberg, H. H., Duimel-Peeters, I. G., Meijer, K., Henry, R. M., Stehouwer, C. D., et al. (2011). Peripheral neuropathy, decreased muscle strength and obesity are strongly associated with walking in persons with type 2 diabetes without manifest mobility limitations. Diabetes Res. Clin. Pract. 91, 32-39. doi: 10.1016/j.diabres.2010.09.030
161. Velloso, C. P. (2008). Regulation of muscle mass by growth hormone and IGF-I. Br. J. Pharmacol. 154, 557-568. doi: 10.1038/bjp.2008.153
162. Vernejoul, M. C. D., Collet, C., and Achengli, Y. C. (2012). Serotonin: good or bad for bone. Bonekey Rep. 1:120. doi: 10.1159/000443031
163. Wang, C., Jackson, G., Jones, T. H., Matsumoto, A. M., Nehra, A., Perelman, M. A., et al. (2011). Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care 34, 1669-1675. doi: 10.2337/dc10-2339
164. Wang, D. T., Yin, Y., Yang, Y. J., Lv, P. J., Shi, Y., Lu, L., et al. (2014). B. Resveratrol prevents TNF-a-induced muscle atrophy via regulation of Akt/mTOR/FoxO1 signaling in C2C12 myotubes. Int. Immunopharmacol. 19, 206-213. doi: 10.1016/j.intimp.2014.02.002
165. Wang, H., Liu, D., Cao, P., Lecker, S., and Hu, Z. (2010). Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine. Diabetes 59, 1879-1889. doi: 10.2337/db10-0207
166. Wang, Z., Li, H., Zhang, D., Liu, X., Zhao, F., Pang, X., et al. (2015). Effect of advanced glycosylation end products on apoptosis in human adipose tissue-derived stem cells in vitro. Cell Biosci. 5:3. doi: 10.1186/2045-3701-5-3
167. Weber, M. M. (2002). Effects of growth hormone on skeletal muscle. Horm. Res. 58, 43-48. doi: 10.1159/000066482
168. Wei, Y., Sowers, J. R., Nistala, R., Gong, H., Uptergrove, G. M., Clark, S. E., et al. (2006). Angiotensin II-induced NADPH oxidase activation impairs insulin signaling in skeletal muscle cells. J. Biol. Chem. 281, 35137-35146. doi: 10.1074/jbc.M601320200
169. Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., and Ferrante, A. W. Jr. (2003). Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796-1808. doi: 10.1172/JCI200319246
170. Williamson, D. L., Li, Z., Tuder, R. M., Feinstein, E., Kimball, S. R., and Dungan, C. M. (2014). Altered nutrient response of mTORC1 as a result of changes in REDD1 expression: effect of obesity vs. REDD1 deficiency. J. Appl. Physiol. 117, 246-256. doi: 10.1152/japplphysiol.01350.2013
171. Xiao, Y., Cui, J., Shi, Y. H., Sun, J., Wang, Z. P., and Le, G. W. (2010). Effects of duodenal redox status on calcium absorption and related genes expression in high-fat diet-fed mice. Nutrition 26, 1188-1194. doi: 10.1016/j.nut.2009.11.021
172. Xu, F., Du, Y., Hang, S., Chen, A., Guo, F., and Xu, T. (2013). Adipocytes regulate the bone marrow microenvironment in a mouse model of obesity. Mol. Med. Rep. 8, 823-828. doi: 10.3892/mmr.2013.1572
173. Yang, D. H., Chiang, T. I., Chang, I. C., Lin, F. H., Wei, C. C., and Cheng, Y. W. (2014). Increased levels of circulating advanced glycation end products in menopausal women with osteoporosis. Int. J. Med. Sci. 11, 453-460. doi: 10.7150/ijms.8172
174. Yang, M., Sun, J., Zhang, T., Liu, J., Zhang, J., Shi, M. A., et al. (2008). Deficiency and inhibition of cathepsin K reduce body weight gain and increase glucose metabolism in mice. Arterioscler. Thromb. Vasc. Biol. 28, 2202-2208. doi: 10.1161/ATVBAHA.108.172320
175. Yang, Z., Hulver, M., McMillan, R. P., Cai, L., Kershaw, E. E., Yu, L., et al. (2012). Regulation of insulin and leptin signaling by muscle suppressor of cytokine signaling 3 (SOCS3). PLoS ONE 7:e47493. doi: 10.1371/journal.pone.0047493
176. Yoshida, T., Tabony, A. M., Galvez, S., Mitch, W. E., Higashi, Y., Sukhanov, S., et al. (2013). Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia. Int. J. Biochem. Cell. Biol. 45, 2322-2332. doi: 10.1016/j.biocel.2013.05.035
177. Yun, S. I., Yoon, H. Y., Jeong, S. Y., and Chung, Y. S. (2009). Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3β. J. Bone Miner. Metab. 27, 140-148. doi: 10.1007/s00774-008-0019-5
178. Zhang, L., Meng, S., Tu, Q., Yu, L., Tang, Y., Dard, M. M., et al. (2014). Adiponectin ameliorates experimental periodontitis in diet-induced obesity mice. PLoS ONE 9:e97824. doi: 10.1371/journal.pone.0097824
179. Zhang, R., Edwards, J. R., Ko, S. Y., Dong, S., Liu, H., Oyajobi, B. O., et al. (2011). Transcriptional regulation of BMP2 expression by the PTH-CREB signaling pathway in osteoblasts. PLoS ONE 6:e20780. doi: 10.1371/journal.pone.0020780
180. Zhang, Y., Zhang, D. Y., Zhao, Y. F., Wang, J., He, J. W., and Luo, J. (2013). Analysis and characterization of the functional TGFβ receptors required for BMP6-induced osteogenic differentiation of mesenchymal progenitor cells. BMB Rep. 46, 107-112. doi: 10.5483/BMBRep.2013.46.2.141