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Coupling factors involved in preserving bone balance

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Abstract

Coupling during bone remodeling refers to the spatial and temporal coordination of bone resorption with bone formation. Studies have assessed the subtle interactions between osteoclasts and osteoblasts to preserve bone balance. Traditionally, coupling research related to osteoclast function has focused on bone resorption activity causing the release of growth factors embedded in the bone matrix. However, considerable evidence from in vitro, animal, and human studies indicates the importance of the osteoclasts themselves in coupling phenomena, and many osteoclast-derived coupling factors have been identified. These include sphingosine-1-phosphate, vesicular–receptor activator of nuclear factor-κB, collagen triple helix repeat containing 1, and cardiotrophin-1. Interestingly, neuronal guidance molecules, such as slit guidance ligand 3, semaphorin (SEMA) 3A, SEMA4D, and netrin-1, originally identified as instructive cues allowing the navigation of growing axons to their targets, have been shown to be involved in the intercellular cross-talk among bone cells. This review discusses osteoclast–osteoblast coupling signals, including recent advances and the potential roles of these signals as therapeutic targets for osteoporosis and as biomarkers predicting human bone health.

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References

  1. Sims NA, Martin TJ (2014) Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep 3:481. https://doi.org/10.1038/bonekey.2013.215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sims NA, Walsh NC (2012) Intercellular cross-talk among bone cells: new factors and pathways. Curr Osteoporos Rep 10:109–117. https://doi.org/10.1007/s11914-012-0096-1

    Article  PubMed  Google Scholar 

  3. Matsuo K, Irie N (2008) Osteoclast-osteoblast communication. Arch Biochem Biophys 473:201–209. https://doi.org/10.1016/j.abb.2008.03.027

    Article  CAS  PubMed  Google Scholar 

  4. Zaidi M (2007) Skeletal remodeling in health and disease. Nat Med 13:791–801. https://doi.org/10.1038/nm1593

    Article  CAS  PubMed  Google Scholar 

  5. Negishi-Koga T, Takayanagi H (2012) Bone cell communication factors and semaphorins. Bonekey Rep 1:183. https://doi.org/10.1038/bonekey.2012.183

    Article  PubMed  PubMed Central  Google Scholar 

  6. Hattner R, Epker BN, Frost HM (1965) Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling. Nature 206:489–490

    Article  CAS  PubMed  Google Scholar 

  7. Howard GA, Bottemiller BL, Turner RT, Rader JI, Baylink DJ (1981) Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism. Proc Natl Acad Sci USA 78:3204–3208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Delaisse JM (2014) The reversal phase of the bone-remodeling cycle: cellular prerequisites for coupling resorption and formation. Bonekey Rep 3:561. https://doi.org/10.1038/bonekey.2014.56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377:1276–1287. https://doi.org/10.1016/s0140-6736(10)62349-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Andersen TL, Sondergaard TE, Skorzynska KE, Dagnaes-Hansen F, Plesner TL, Hauge EM, Plesner T, Delaisse JM (2009) A physical mechanism for coupling bone resorption and formation in adult human bone. Am J Pathol 174:239–247. https://doi.org/10.2353/ajpath.2009.080627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Reyes C, Hitz M, Prieto-Alhambra D, Abrahamsen B (2016) Risks and benefits of bisphosphonate therapies. J Cell Biochem 117:20–28. https://doi.org/10.1002/jcb.25266

    Article  CAS  PubMed  Google Scholar 

  12. Canalis E, Giustina A, Bilezikian JP (2007) Mechanisms of anabolic therapies for osteoporosis. N Engl J Med 357:905–916. https://doi.org/10.1056/NEJMra067395

    Article  CAS  PubMed  Google Scholar 

  13. Neer RM, Arnaud CD, Zanchetta JR et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441. https://doi.org/10.1056/nejm200105103441904

    Article  CAS  PubMed  Google Scholar 

  14. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342. https://doi.org/10.1038/nature01658

    Article  CAS  PubMed  Google Scholar 

  15. Sims NA, Martin TJ (2015) Coupling signals between the osteoclast and osteoblast: how are messages transmitted between these temporary visitors to the bone surface? Front Endocrinol (Lausanne) 6:41. https://doi.org/10.3389/fendo.2015.00041

    Article  Google Scholar 

  16. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL (2000) The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Mineral Res 15:2–12. https://doi.org/10.1359/jbmr.2000.15.1.2

    Article  CAS  Google Scholar 

  17. Henriksen K, Karsdal MA, Martin TJ (2014) Osteoclast-derived coupling factors in bone remodeling. Calcif Tissue Int 94:88–97. https://doi.org/10.1007/s00223-013-9741-7

    Article  CAS  PubMed  Google Scholar 

  18. Centrella M, Canalis E (1985) Local regulators of skeletal growth: a perspective. Endocr Rev 6:544–551. https://doi.org/10.1210/edrv-6-4-544

    Article  CAS  PubMed  Google Scholar 

  19. Tsukamoto T, Matsui T, Fukase M, Fujita T (1991) Platelet-derived growth factor B chain homodimer enhances chemotaxis and DNA synthesis in normal osteoblast-like cells (MC3T3-E1). Biochem Biophys Res Commun 175:745–751

    Article  CAS  PubMed  Google Scholar 

  20. Oreffo RO, Mundy GR, Seyedin SM, Bonewald LF (1989) Activation of the bone-derived latent TGF beta complex by isolated osteoclasts. Biochem Biophys Res Commun 158:817–823

    Article  CAS  PubMed  Google Scholar 

  21. Hock JM, Canalis E, Centrella M (1990) Transforming growth factor-beta stimulates bone matrix apposition and bone cell replication in cultured fetal rat calvariae. Endocrinology 126:421–426. https://doi.org/10.1210/endo-126-1-421

    Article  CAS  PubMed  Google Scholar 

  22. Bonewald LF, Mundy GR (1990) Role of transforming growth factor-beta in bone remodeling. Clin Orthop Relat Res 250:261–276

    Google Scholar 

  23. Crane JL, Cao X (2014) Bone marrow mesenchymal stem cells and TGF-beta signaling in bone remodeling. J Clin Invest 124:466–472. https://doi.org/10.1172/jci70050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hanamura H, Higuchi Y, Nakagawa M, Iwata H, Nogami H, Urist MR (1980) Solubilized bone morphogenetic protein (BMP) from mouse osteosarcoma and rat demineralized bone matrix. Clin Orthop Relat Res 148:281–290

    CAS  Google Scholar 

  25. Mohan S, Baylink DJ (1996) Insulin-like growth factor system components and the coupling of bone formation to resorption. Horm Res 45(Suppl 1):59–62. https://doi.org/10.1159/000184833

    Article  CAS  PubMed  Google Scholar 

  26. Mayr-Wohlfart U, Waltenberger J, Hausser H, Kessler S, Gunther KP, Dehio C, Puhl W, Brenner RE (2002) Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone 30:472–477

    Article  CAS  PubMed  Google Scholar 

  27. Tang Y, Wu X, Lei W et al (2009) TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med 15:757–765. https://doi.org/10.1038/nm.1979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Xian L, Wu X, Pang L et al (2012) Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat Med 18:1095–1101. https://doi.org/10.1038/nm.2793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Crane JL, Xian L, Cao X (2016) Role of TGF-beta signaling in coupling bone remodeling. Methods Mol Biol 1344:287–300. https://doi.org/10.1007/978-1-4939-2966-5_18

    Article  CAS  PubMed  Google Scholar 

  30. Dallas SL, Park-Snyder S, Miyazono K, Twardzik D, Mundy GR, Bonewald LF (1994) Characterization and autoregulation of latent transforming growth factor beta (TGF beta) complexes in osteoblast-like cell lines. Production of a latent complex lacking the latent TGF beta-binding protein. J Biol Chem 269:6815–6821

    CAS  PubMed  Google Scholar 

  31. Pfeilschifter J, Bonewald L, Mundy GR (1990) Characterization of the latent transforming growth factor beta complex in bone. J Bone Mineral Res 5:49–58. https://doi.org/10.1002/jbmr.5650050109

    Article  CAS  Google Scholar 

  32. Dallas SL, Rosser JL, Mundy GR, Bonewald LF (2002) Proteolysis of latent transforming growth factor-beta (TGF-beta)-binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-beta from bone matrix. J Biol Chem 277:21352–21360. https://doi.org/10.1074/jbc.M111663200

    Article  CAS  PubMed  Google Scholar 

  33. Martin TJ, Sims NA (2005) Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med 11:76–81. https://doi.org/10.1016/j.molmed.2004.12.004

    Article  CAS  PubMed  Google Scholar 

  34. Karsdal MA, Martin TJ, Bollerslev J, Christiansen C, Henriksen K (2007) Are nonresorbing osteoclasts sources of bone anabolic activity? J Bone Mineral Res 22:487–494. https://doi.org/10.1359/jbmr.070109

    Article  CAS  Google Scholar 

  35. Karsdal MA, Neutzsky-Wulff AV, Dziegiel MH, Christiansen C, Henriksen K (2008) Osteoclasts secrete non-bone derived signals that induce bone formation. Biochem Biophys Res Commun 366:483–488. https://doi.org/10.1016/j.bbrc.2007.11.168

    Article  CAS  PubMed  Google Scholar 

  36. Kreja L, Brenner RE, Tautzenberger A, Liedert A, Friemert B, Ehrnthaller C, Huber-Lang M, Ignatius A (2010) Non-resorbing osteoclasts induce migration and osteogenic differentiation of mesenchymal stem cells. J Cell Biochem 109:347–355. https://doi.org/10.1002/jcb.22406

    Article  CAS  PubMed  Google Scholar 

  37. Henriksen K, Andreassen KV, Thudium CS et al (2012) A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts. Bone 51:353–361. https://doi.org/10.1016/j.bone.2012.06.007

    Article  CAS  PubMed  Google Scholar 

  38. Kim BJ, Lee YS, Lee SY et al (2012) Afamin secreted from nonresorbing osteoclasts acts as a chemokine for preosteoblasts via the Akt-signaling pathway. Bone 51:431–440. https://doi.org/10.1016/j.bone.2012.06.015

    Article  CAS  PubMed  Google Scholar 

  39. Segovia-Silvestre T, Neutzsky-Wulff AV, Sorensen MG, Christiansen C, Bollerslev J, Karsdal MA, Henriksen K (2009) Advances in osteoclast biology resulting from the study of osteopetrotic mutations. Hum Genet 124:561–577. https://doi.org/10.1007/s00439-008-0583-8

    Article  CAS  PubMed  Google Scholar 

  40. Thudium CS, Moscatelli I, Flores C, Thomsen JS, Bruel A, Gudmann NS, Hauge EM, Karsdal MA, Richter J, Henriksen K (2014) A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation. Calcif Tissue Int 95:83–93. https://doi.org/10.1007/s00223-014-9865-4

    Article  CAS  PubMed  Google Scholar 

  41. Sobacchi C, Schulz A, Coxon FP, Villa A, Helfrich MH (2013) Osteopetrosis: genetics, treatment and new insights into osteoclast function. Nat Rev Endocrinol 9:522–536. https://doi.org/10.1038/nrendo.2013.137

    Article  CAS  PubMed  Google Scholar 

  42. Teti A, Econs MJ (2017) Osteopetroses, emphasizing potential approaches to treatment. Bone 102:50–59. https://doi.org/10.1016/j.bone.2017.02.002

    Article  CAS  PubMed  Google Scholar 

  43. Del Fattore A, Peruzzi B, Rucci N et al (2006) Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment. J Med Genet 43:315–325. https://doi.org/10.1136/jmg.2005.036673

    Article  CAS  PubMed  Google Scholar 

  44. Bollerslev J, Steiniche T, Melsen F, Mosekilde L (1989) Structural and histomorphometric studies of iliac crest trabecular and cortical bone in autosomal dominant osteopetrosis: a study of two radiological types. Bone 10:19–24

    Article  CAS  PubMed  Google Scholar 

  45. Stoch SA, Wagner JA (2008) Cathepsin K inhibitors: a novel target for osteoporosis therapy. Clin Pharmacol Ther 83:172–176. https://doi.org/10.1038/sj.clpt.6100450

    Article  CAS  PubMed  Google Scholar 

  46. Stoch SA, Zajic S, Stone J et al (2009) Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies. Clin Pharmacol Ther 86:175–182. https://doi.org/10.1038/clpt.2009.60

    Article  CAS  PubMed  Google Scholar 

  47. Bone HG, McClung MR, Roux C, Recker RR, Eisman JA, Verbruggen N, Hustad CM, DaSilva C, Santora AC, Ince BA (2010) Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Mineral Res 25:937–947. https://doi.org/10.1359/jbmr.091035

    Article  Google Scholar 

  48. Duong LT (2012) Therapeutic inhibition of cathepsin K-reducing bone resorption while maintaining bone formation. Bonekey Rep 1:67. https://doi.org/10.1038/bonekey.2012.67

    Article  PubMed  PubMed Central  Google Scholar 

  49. Jensen PR, Andersen TL, Pennypacker BL, Duong LT, Delaisse JM (2014) The bone resorption inhibitors odanacatib and alendronate affect post-osteoclastic events differently in ovariectomized rabbits. Calcif Tissue Int 94:212–222. https://doi.org/10.1007/s00223-013-9800-0

    Article  CAS  PubMed  Google Scholar 

  50. Sims NA, Martin TJ, Quinn JMW (2015) Chapter 10—coupling: the influences of immune and bone cells. In: Lorenzo J, Horowitz M, Choi Y, Takayanagi H, Schett G (eds) Osteoimmunology: interactions of the immune and skeletal systems, 2nd edn. Elsevier, Academic Press, Amsterdam, pp 169–185. https://doi.org/10.1016/b978-0-12-800571-2.00010-4

    Chapter  Google Scholar 

  51. Zhu S, Yao F, Qiu H, Zhang G, Xu H, Xu J (2018) Coupling factors and exosomal packaging microRNAs involved in the regulation of bone remodelling. Biol Rev Camb Philos Soc 93:469–480. https://doi.org/10.1111/brv.12353

    Article  PubMed  Google Scholar 

  52. Kidd T, Bland KS, Goodman CS (1999) Slit is the midline repellent for the robo receptor in Drosophila. Cell 96:785–794

    Article  CAS  PubMed  Google Scholar 

  53. Kim BJ, Lee YS, Lee SY et al (2018) Osteoclast-secreted SLIT3 coordinates bone resorption and formation. J Clin Invest 128:1429–1441. https://doi.org/10.1172/jci91086

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kong YY, Yoshida H, Sarosi I et al (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315–323. https://doi.org/10.1038/16852

    Article  CAS  PubMed  Google Scholar 

  55. Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O’Brien CA (2011) Matrix-embedded cells control osteoclast formation. Nat Med 17:1235–1241. https://doi.org/10.1038/nm.2448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ikebuchi Y, Aoki S, Honma M et al (2018) Coupling of bone resorption and formation by RANKL reverse signalling. Nature 561:195–200. https://doi.org/10.1038/s41586-018-0482-7

    Article  CAS  PubMed  Google Scholar 

  57. Zaidi M, Cardozo CP (2018) Receptor becomes a ligand to control bone remodelling. Nature 561:180–181. https://doi.org/10.1038/d41586-018-05960-x

    Article  CAS  PubMed  Google Scholar 

  58. Rosen H, Goetzl EJ (2005) Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol 5:560–570. https://doi.org/10.1038/nri1650

    Article  CAS  PubMed  Google Scholar 

  59. Meshcheryakova A, Mechtcheriakova D, Pietschmann P (2017) Sphingosine 1-phosphate signaling in bone remodeling: multifaceted roles and therapeutic potential. Expert Opin Ther Targets 21:725–737. https://doi.org/10.1080/14728222.2017.1332180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ryu J, Kim HJ, Chang EJ, Huang H, Banno Y, Kim HH (2006) Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast-osteoblast coupling. EMBO J 25:5840–5851. https://doi.org/10.1038/sj.emboj.7601430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Grey A, Xu X, Hill B, Watson M, Callon K, Reid IR, Cornish J (2004) Osteoblastic cells express phospholipid receptors and phosphatases and proliferate in response to sphingosine-1-phosphate. Calcif Tissue Int 74:542–550. https://doi.org/10.1007/s00223-003-0155-9

    Article  CAS  PubMed  Google Scholar 

  62. Pederson L, Ruan M, Westendorf JJ, Khosla S, Oursler MJ (2008) Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci USA 105:20764–20769. https://doi.org/10.1073/pnas.0805133106

    Article  PubMed  PubMed Central  Google Scholar 

  63. Roelofsen T, Akkers R, Beumer W, Apotheker M, Steeghs I, van de Ven J, Gelderblom C, Garritsen A, Dechering K (2008) Sphingosine-1-phosphate acts as a developmental stage specific inhibitor of platelet-derived growth factor-induced chemotaxis of osteoblasts. J Cell Biochem 105:1128–1138. https://doi.org/10.1002/jcb.21915

    Article  CAS  PubMed  Google Scholar 

  64. Grey A, Chen Q, Callon K, Xu X, Reid IR, Cornish J (2002) The phospholipids sphingosine-1-phosphate and lysophosphatidic acid prevent apoptosis in osteoblastic cells via a signaling pathway involving G(i) proteins and phosphatidylinositol-3 kinase. Endocrinology 143:4755–4763. https://doi.org/10.1210/en.2002-220347

    Article  CAS  PubMed  Google Scholar 

  65. Lotinun S, Kiviranta R, Matsubara T et al (2013) Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation. J Clin Invest 123:666–681. https://doi.org/10.1172/JCI64840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ishii M, Egen JG, Klauschen F, Meier-Schellersheim M, Saeki Y, Vacher J, Proia RL, Germain RN (2009) Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature 458:524–528. https://doi.org/10.1038/nature07713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ishii M, Kikuta J, Shimazu Y, Meier-Schellersheim M, Germain RN (2010) Chemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivo. J Exp Med 207:2793–2798. https://doi.org/10.1084/jem.20101474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Takeshita S, Fumoto T, Matsuoka K, Park KA, Aburatani H, Kato S, Ito M, Ikeda K (2013) Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation. J Clin Invest 123:3914–3924. https://doi.org/10.1172/jci69493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Matsuoka K, Kohara Y, Naoe Y, Watanabe A, Ito M, Ikeda K, Takeshita S (2018) WAIF1 is a cell-surface CTHRC1 binding protein coupling bone resorption and formation. J Bone Mineral Res 33:1500–1512. https://doi.org/10.1002/jbmr.3436

    Article  CAS  Google Scholar 

  70. Sims NA, Jenkins BJ, Quinn JM, Nakamura A, Glatt M, Gillespie MT, Ernst M, Martin TJ (2004) Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways. J Clin Invest 113:379–389. https://doi.org/10.1172/jci19872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Walker EC, McGregor NE, Poulton IJ, Pompolo S, Allan EH, Quinn JM, Gillespie MT, Martin TJ, Sims NA (2008) Cardiotrophin-1 is an osteoclast-derived stimulus of bone formation required for normal bone remodeling. J Bone Mineral Res 23:2025–2032. https://doi.org/10.1359/jbmr.080706

    Article  CAS  Google Scholar 

  72. Sims NA, Walsh NC (2010) GP130 cytokines and bone remodelling in health and disease. BMB Rep 43:513–523

    Article  CAS  PubMed  Google Scholar 

  73. Matsuoka K, Park KA, Ito M, Ikeda K, Takeshita S (2014) Osteoclast-derived complement component 3a stimulates osteoblast differentiation. J Bone Mineral Res 29:1522–1530. https://doi.org/10.1002/jbmr.2187

    Article  CAS  Google Scholar 

  74. Sanchez-Fernandez MA, Gallois A, Riedl T, Jurdic P, Hoflack B (2008) Osteoclasts control osteoblast chemotaxis via PDGF-BB/PDGF receptor beta signaling. PLoS One 3:e3537. https://doi.org/10.1371/journal.pone.0003537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Pasterkamp RJ, Kolodkin AL (2013) SnapShot: axon guidance. Cell 153:494, 494e491–492. https://doi.org/10.1016/j.cell.2013.03.031

  76. Van Battum EY, Brignani S, Pasterkamp RJ (2015) Axon guidance proteins in neurological disorders. Lancet Neurol 14:532–546. https://doi.org/10.1016/S1474-4422(14)70257-1

    Article  CAS  PubMed  Google Scholar 

  77. Geutskens SB, Hordijk PL, van Hennik PB (2010) The chemorepellent Slit3 promotes monocyte migration. J Immunol 185:7691–7698. https://doi.org/10.4049/jimmunol.0903898

    Article  CAS  PubMed  Google Scholar 

  78. Arese M, Serini G, Bussolino F (2011) Nervous vascular parallels: axon guidance and beyond. Int J Dev Biol 55:439–445. https://doi.org/10.1387/ijdb.103242ma

    Article  CAS  PubMed  Google Scholar 

  79. Suzuki K, Kumanogoh A, Kikutani H (2008) Semaphorins and their receptors in immune cell interactions. Nat Immunol 9:17–23. https://doi.org/10.1038/ni1553

    Article  CAS  PubMed  Google Scholar 

  80. Pasquale EB (2005) Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 6:462–475. https://doi.org/10.1038/nrm1662

    Article  CAS  PubMed  Google Scholar 

  81. Pasquale EB (2008) Eph-ephrin bidirectional signaling in physiology and disease. Cell 133:38–52. https://doi.org/10.1016/j.cell.2008.03.011

    Article  CAS  PubMed  Google Scholar 

  82. Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K (2006) Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab 4:111–121. https://doi.org/10.1016/j.cmet.2006.05.012

    Article  CAS  PubMed  Google Scholar 

  83. Andersen TL, Abdelgawad ME, Kristensen HB, Hauge EM, Rolighed L, Bollerslev J, Kjaersgaard-Andersen P, Delaisse JM (2013) Understanding coupling between bone resorption and formation: are reversal cells the missing link? Am J Pathol 183:235–246. https://doi.org/10.1016/j.ajpath.2013.03.006

    Article  CAS  PubMed  Google Scholar 

  84. Castellani V, Rougon G (2002) Control of semaphorin signaling. Curr Opin Neurobiol 12:532–541

    Article  CAS  PubMed  Google Scholar 

  85. Epstein JA, Aghajanian H, Singh MK (2015) Semaphorin signaling in cardiovascular development. Cell Metab 21:163–173. https://doi.org/10.1016/j.cmet.2014.12.015

    Article  CAS  PubMed  Google Scholar 

  86. Jongbloets BC, Pasterkamp RJ (2014) Semaphorin signalling during development. Development 141:3292–3297. https://doi.org/10.1242/dev.105544

    Article  CAS  PubMed  Google Scholar 

  87. Takamatsu H, Okuno T, Kumanogoh A (2010) Regulation of immune cell responses by semaphorins and their receptors. Cell Mol Immunol 7:83–88. https://doi.org/10.1038/cmi.2009.111

    Article  PubMed  PubMed Central  Google Scholar 

  88. Verlinden L, Vanderschueren D, Verstuyf A (2016) Semaphorin signaling in bone. Mol Cell Endocrinol 432:66–74. https://doi.org/10.1016/j.mce.2015.09.009

    Article  CAS  PubMed  Google Scholar 

  89. Dacquin R, Domenget C, Kumanogoh A, Kikutani H, Jurdic P, Machuca-Gayet I (2011) Control of bone resorption by semaphorin 4D is dependent on ovarian function. PLoS One 6:e26627. https://doi.org/10.1371/journal.pone.0026627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Negishi-Koga T, Shinohara M, Komatsu N, Bito H, Kodama T, Friedel RH, Takayanagi H (2011) Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nat Med 17:1473–1480. https://doi.org/10.1038/nm.2489

    Article  CAS  PubMed  Google Scholar 

  91. Furuya M, Kikuta J, Fujimori S et al (2018) Direct cell-cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo. Nat Commun 9:300. https://doi.org/10.1038/s41467-017-02541-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Hayashi M, Nakashima T, Taniguchi M, Kodama T, Kumanogoh A, Takayanagi H (2012) Osteoprotection by semaphorin 3A. Nature 485:69–74. https://doi.org/10.1038/nature11000

    Article  CAS  PubMed  Google Scholar 

  93. Fukuda T, Takeda S, Xu R et al (2013) Sema3A regulates bone-mass accrual through sensory innervations. Nature 497:490–493. https://doi.org/10.1038/nature12115

    Article  CAS  PubMed  Google Scholar 

  94. Iqbal J, Yuen T, Kim SM, Zaidi M (2018) Opening windows for bone remodeling through a SLIT. J Clin Invest 128:1255–1257. https://doi.org/10.1172/jci120325

    Article  PubMed  PubMed Central  Google Scholar 

  95. Mediero A, Ramkhelawon B, Perez-Aso M, Moore KJ, Cronstein BN (2015) Netrin-1 is a critical autocrine/paracrine factor for osteoclast differentiation. J Bone Mineral Res 30:837–854. https://doi.org/10.1002/jbmr.2421

    Article  CAS  Google Scholar 

  96. Stoeckli ET (2018) Understanding axon guidance: are we nearly there yet? Development. https://doi.org/10.1242/dev.151415

    Article  PubMed  Google Scholar 

  97. Wein W (2016) Drug development: successes, problems and pitfalls-the industry perspective. ESMO Open 1:e000033. https://doi.org/10.1136/esmoopen-2016-000033

    Article  PubMed  PubMed Central  Google Scholar 

  98. Drake MT, Clarke BL, Oursler MJ, Khosla S (2017) Cathepsin K inhibitors for osteoporosis: biology, potential clinical utility, and lessons learned. Endocr Rev 38:325–350. https://doi.org/10.1210/er.2015-1114

    Article  PubMed  PubMed Central  Google Scholar 

  99. Gauthier JY, Chauret N, Cromlish W et al (2008) The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett 18:923–928. https://doi.org/10.1016/j.bmcl.2007.12.047

    Article  CAS  PubMed  Google Scholar 

  100. Bone HG, Dempster DW, Eisman JA et al (2015) Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the Long-Term Odanacatib Fracture Trial. Osteoporos Int 26:699–712. https://doi.org/10.1007/s00198-014-2944-6

    Article  CAS  PubMed  Google Scholar 

  101. Chapurlat RD (2015) Odanacatib: a review of its potential in the management of osteoporosis in postmenopausal women. Ther Adv Musculoskelet Dis 7:103–109. https://doi.org/10.1177/1759720x15580903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Mullard A (2016) Merck & Co. drops osteoporosis drug odanacatib. Nat Rev Drug Discov 15:669. https://doi.org/10.1038/nrd.2016.207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Ryu TK, Kang RH, Jeong KY, Jun DR, Koh JM, Kim D, Bae SK, Choi SW (2016) Bone-targeted delivery of nanodiamond-based drug carriers conjugated with alendronate for potential osteoporosis treatment. J Control Release 232:152–160. https://doi.org/10.1016/j.jconrel.2016.04.025

    Article  CAS  PubMed  Google Scholar 

  104. Lee SH, Lee SY, Lee YS, Kim BJ, Lim KH, Cho EH, Kim SW, Koh JM, Kim GS (2012) Higher circulating sphingosine 1-phosphate levels are associated with lower bone mineral density and higher bone resorption marker in humans. J Clin Endocrinol Metab 97:E1421–E1428. https://doi.org/10.1210/jc.2012-1044

    Article  CAS  PubMed  Google Scholar 

  105. Kim BJ, Shin KO, Kim H, Ahn SH, Lee SH, Seo CH, Byun SE, Chang JS, Koh JM, Lee YM (2016) The effect of sphingosine-1-phosphate on bone metabolism in humans depends on its plasma/bone marrow gradient. J Endocrinol Invest 39:297–303. https://doi.org/10.1007/s40618-015-0364-x

    Article  CAS  PubMed  Google Scholar 

  106. Liu DM, Lu N, Zhao L et al (2014) Serum Sema3A is in a weak positive association with bone formation marker osteocalcin but not related to bone mineral densities in postmenopausal women. J Clin Endocrinol Metab 99:E2504–E2509. https://doi.org/10.1210/jc.2014-1443

    Article  CAS  PubMed  Google Scholar 

  107. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24:23–57. https://doi.org/10.1007/s00198-012-2074-y

    Article  CAS  PubMed  Google Scholar 

  108. Sornay-Rendu E, Munoz F, Garnero P, Duboeuf F, Delmas PD (2005) Identification of osteopenic women at high risk of fracture: the OFELY study. J Bone Mineral Res 20:1813–1819. https://doi.org/10.1359/jbmr.050609

    Article  Google Scholar 

  109. Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA (2004) Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 34:195–202

    Article  CAS  PubMed  Google Scholar 

  110. Bae SJ, Lee SH, Ahn SH, Kim HM, Kim BJ, Koh JM (2016) The circulating sphingosine-1-phosphate level predicts incident fracture in postmenopausal women: a 3.5-year follow-up observation study. Osteoporos Int 27:2533–2541. https://doi.org/10.1007/s00198-016-3565-z

    Article  CAS  PubMed  Google Scholar 

  111. Ardawi MM, Rouzi AA, Al-Senani NS, Qari MH, Elsamanoudy AZ, Mousa SA (2018) High plasma sphingosine 1-phosphate levels predict osteoporotic fractures in postmenopausal women: the Center of Excellence for Osteoporosis Research study. J Bone Metab 25:87–98. https://doi.org/10.11005/jbm.2018.25.2.87

    Article  PubMed  PubMed Central  Google Scholar 

  112. Lassen NE, Andersen TL, Ploen GG, Soe K, Hauge EM, Harving S, Eschen GET, Delaisse JM (2017) Coupling of bone resorption and formation in real time: new knowledge gained from human haversian BMUs. J Bone Mineral Res 32:1395–1405. https://doi.org/10.1002/jbmr.3091

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Mark W. Hamrick at the Medical College of Georgia, Augusta University (Augusta, GA, USA) for his helpful comments. This study was supported by grants from the Bio & Medical Technology Development Program of the National Research Foundation, funded by the Korean government, MSIP (project no. 2016M3A9E8941329), and from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (project nos. HI15C2792 and HI15C0377).

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  1. Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea

    Beom-Jun Kim & Jung-Min Koh

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  1. Beom-Jun Kim
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BK and JK summarized the literature and wrote the paper. Both authors read and approved the final manuscript.

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Correspondence to Jung-Min Koh.

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The authors declare that they have patents on S1P as a biomarker and SLIT3 as a therapeutic target for osteoporosis.

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Kim, BJ., Koh, JM. Coupling factors involved in preserving bone balance. Cell. Mol. Life Sci. 76, 1243–1253 (2019). https://doi.org/10.1007/s00018-018-2981-y

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