Osteoclasts Provide Coupling Signals to Osteoblast Lineage Cells Through Multiple Mechanisms

Literature Cited

1. 1. 

   Frost HM. 1964. Dynamics of bone remodeling. Bone Biodynamics HM Frost 315–33 Boston: Little, Brown, & Co.
   [Google Scholar]
2. 2. 

   Parfitt A. 1983. Bone histomorphometry: techniques and interpretations. Histomorphometry RR Recker 142–221 Baton Rouge, LA: CRC Press
   [Google Scholar]
3. 3. 

   Robling AG, Turner CH. 2009. Mechanical signaling for bone modeling and remodeling. Crit. Rev. Eukaryot. Gene Expr. 19:319–38
   [Google Scholar]
4. 4. 

   Hattner R, Epker BN, Frost HM 1965. Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling. Nature 206:489–90
   [Google Scholar]
5. 5. 

   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
   [Google Scholar]
6. 6. 

   Parfitt AM. 2001. The bone remodeling compartment: a circulatory function for bone lining cells. J. Bone Miner. Res. 16:1583–85
   [Google Scholar]
7. 7. 

   Parfitt AM. 1982. The coupling of bone formation to bone resorption: a critical analysis of the concept and of its relevance to the pathogenesis of osteoporosis. Metab. Bone Dis. Relat. Res. 4:1–6
   [Google Scholar]
8. 8. 

   Eriksen EF. 1986. Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. Endocr. Rev. 7:379–408
   [Google Scholar]
9. 9. 

   Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F 2001. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J. Bone Miner. Res. 16:1575–82
   [Google Scholar]
10. 10. 

    Eriksen EF, Vesterby A, Kassem M, Melsen F, Mosekilde L 1993. Bone remodeling and bone structure. Physiology and Pharmacology of Bone GR Mundy, TJ Martin 67–109 Berlin: Springer Verlag
    [Google Scholar]
11. 11. 

    Baron R. 1977. Importance of the intermediate phase between resorption and formation in the measurement and understanding of the bone remodelling sequence. I. Bone Remodelling P Meunier 179–83 Paris: Lab Armour Montague
    [Google Scholar]
12. 12. 

    Winkler IG, Sims NA, Pettit AR, Barbier V, Nowlan B et al. 2010. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood 116:4815–28
    [Google Scholar]
13. 13. 

    Andreasen CM, Ding M, Overgaard S, Bollen P, Andersen TL 2015. A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep. Bone 75:32–39
    [Google Scholar]
14. 14. 

    Mackie EJ, Tatarczuch L, Mirams M 2011. The skeleton: a multi-functional complex organ: the growth plate chondrocyte and endochondral ossification. J. Endocrinol. 211:109–21
    [Google Scholar]
15. 15. 

    Rauch F. 2012. The dynamics of bone structure development during pubertal growth. J. Musculoskelet. Neuronal Interact. 12:1–6
    [Google Scholar]
16. 16. 

    Sims NA, Ng KW. 2014. Implications of osteoblast-osteoclast interactions in the management of osteoporosis by antiresorptive agents denosumab and odanacatib. Curr. Osteoporos. Rep. 12:98–106
    [Google Scholar]
17. 17. 

    Seeman E, Martin TJ. 2019. Antiresorptive and anabolic agents in the prevention and reversal of bone fragility. Nat. Rev. Rheumatol. 15:225–36
    [Google Scholar]
18. 18. 

    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. PNAS 78:3204–8
    [Google Scholar]
19. 19. 

    Tang Y, Wu X, Lei W, Pang L, Wan C et al. 2009. TGF-β1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat. Med. 15:757–65
    [Google Scholar]
20. 20. 

    Xian L, Wu X, Pang L, Lou M, Rosen CJ et al. 2012. Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat. Med. 18:1095–101
    [Google Scholar]
21. 21. 

    Canalis E, Ornitz DM. 2000. Biology of platelet-derived growth factor. Skeletal Growth Factors E Canalis 153–66 Philadelphia, PA: Lippincott Williams & Wilkins
    [Google Scholar]
22. 22. 

    Xie H, Cui Z, Wang L, Xia Z, Hu Y et al. 2014. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat. Med. 20:1270–78
    [Google Scholar]
23. 23. 

    Sims NA, Martin TJ. 2020. Coupling of bone formation and resorption. In Principles of Bone Biologyed. JP Bilezikian, TJ Martin, TL Clemens, C Rosenpp. 219–43. New York: Elsevier. 4th ed.
    [Google Scholar]
24. 24. 

    Sims NA, Jenkins BJ, Quinn JM, Nakamura A, Glatt M et al. 2004. Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways. J. Clin. Investig. 113:379–89
    [Google Scholar]
25. 25. 

    Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA et al. 2001. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344:1434–41
    [Google Scholar]
26. 26. 

    Holtrop ME, King GJ, Cox KA, Reit B 1979. Time-related changes in the ultrastructure of osteoclasts after injection of parathyroid hormone in young rats. Calcif. Tissue Int. 27:129–35
    [Google Scholar]
27. 27. 

    Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA et al. 2003. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N. Engl. J. Med. 349:1207–15
    [Google Scholar]
28. 28. 

    Delmas PD, Vergnaud P, Arlot ME, Pastoureau P, Meunier PJ, Nilssen MH 1995. The anabolic effect of human PTH (1–34) on bone formation is blunted when bone resorption is inhibited by the bisphosphonate tiludronate–is activated resorption a prerequisite for the in vivo effect of PTH on formation in a remodeling system?. Bone 16:603–10
    [Google Scholar]
29. 29. 

    Martin TJ, Sims NA. 2005. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol. Med. 11:76–81
    [Google Scholar]
30. 30. 

    Sobacchi C, Frattini A, Guerrini MM, Abinun M, Pangrazio A et al. 2007. Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nat. Genet. 39:960–62
    [Google Scholar]
31. 31. 

    Frattini A, Vezzoni P, Villa A, Sobacchi C 2007. The dissection of human autosomal recessive osteopetrosis identifies an osteoclast-poor form due to RANKL deficiency. Cell Cycle 6:3027–33
    [Google Scholar]
32. 32. 

    Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R et al. 1994. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266:443–48
    [Google Scholar]
33. 33. 

    Alam I, Gray AK, Chu K, Ichikawa S, Mohammed KS et al. 2014. Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models. Bone 59:66–75
    [Google Scholar]
34. 34. 

    Karsdal MA, Henriksen K, Sorensen MG, Gram J, Schaller S et al. 2005. Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption. Am. J. Pathol. 166:467–76
    [Google Scholar]
35. 35. 

    Henriksen K, Gram J, Schaller S, Dahl BH, Dziegiel MH et al. 2004. Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II. Am. J. Pathol. 164:1537–45
    [Google Scholar]
36. 36. 

    Marzia M, Sims NA, Voit S, Migliaccio S, Taranta A et al. 2000. Decreased c-Src expression enhances osteoblast differentiation and bone formation. J. Cell Biol. 151:311–20
    [Google Scholar]
37. 37. 

    Gil-Henn H, Destaing O, Sims NA, Aoki K, Alles N et al. 2007. Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2^−/− mice. J. Cell Biol. 178:1053–64
    [Google Scholar]
38. 38. 

    Pennypacker B, Shea M, Liu Q, Masarachia P, Saftig P et al. 2009. Bone density, strength, and formation in adult cathepsin K(−/−) mice. Bone 44:199–207
    [Google Scholar]
39. 39. 

    Henriksen K, Flores C, Thomsen JS, Bruel AM, Thudium CS et al. 2011. Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength. PLOS ONE 6:e27482
    [Google Scholar]
40. 40. 

    Del Fattore A, Peruzzi B, Rucci N, Recchia I, Cappariello A et al. 2006. Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment. J. Med. Genet. 43:315–25
    [Google Scholar]
41. 41. 

    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. 366:483–88
    [Google Scholar]
42. 42. 

    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. PNAS 105:20764–69
    [Google Scholar]
43. 43. 

    Henriksen K, Andreassen KV, Thudium CS, Gudmann KN, Moscatelli I et al. 2012. A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts. Bone 51:353–61
    [Google Scholar]
44. 44. 

    Thudium CS, Moscatelli I, Flores C, Thomsen JS, Bruel A et al. 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
    [Google Scholar]
45. 45. 

    Walker EC, McGregor NE, Poulton IJ, Pompolo S, Allan EH et al. 2008. Cardiotrophin-1 is an osteoclast-derived stimulus of bone formation required for normal bone remodeling. J. Bone Miner. Res. 23:2025–32
    [Google Scholar]
46. 46. 

    Walker EC, McGregor NE, Poulton IJ, Solano M, Pompolo S et al. 2010. Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice. J. Clin. Investig. 120:582–92
    [Google Scholar]
47. 47. 

    Richards CD, Langdon C, Deschamps P, Pennica D, Shaughnessy SG 2000. Stimulation of osteoclast differentiation in vitro by mouse oncostatin M, leukaemia inhibitory factor, cardiotrophin-1 and interleukin 6: synergy with dexamethasone. Cytokine 12:613–21
    [Google Scholar]
48. 48. 

    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 25:5840–51
    [Google Scholar]
49. 49. 

    Lotinun S, Kiviranta R, Matsubara T, Alzate JA, Neff L et al. 2013. Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation. J. Clin. Investig. 123:666–81
    [Google Scholar]
50. 50. 

    Alvarez SE, Milstien S, Spiegel S 2007. Autocrine and paracrine roles of sphingosine-1-phosphate. Trends Endocrinol. Metab. 18:300–7
    [Google Scholar]
51. 51. 

    Ishii M, Egen JG, Klauschen F, Meier-Schellersheim M, Saeki Y et al. 2009. Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature 458:524–28
    [Google Scholar]
52. 52. 

    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. 207:2793–98
    [Google Scholar]
53. 53. 

    Weske S, Vaidya M, Reese A, von Wnuck Lipinski K, Keul P et al. 2018. Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss. Nat. Med. 24:667–78
    [Google Scholar]
54. 54. 

    Takeshita S, Fumoto T, Matsuoka K, Park KA, Aburatani H et al. 2013. Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation. J. Clin. Investig. 123:3914–24
    [Google Scholar]
55. 55. 

    Kimura H, Kwan KM, Zhang Z, Deng JM, Darnay BG et al. 2008. Cthrc1 is a positive regulator of osteoblastic bone formation. PLOS ONE 3:e3174
    [Google Scholar]
56. 56. 

    Stohn JP, Perreault NG, Wang Q, Liaw L, Lindner V 2012. Cthrc1, a novel circulating hormone regulating metabolism. PLOS ONE 7:e47142
    [Google Scholar]
57. 57. 

    Lee SH, Rho J, Jeong D, Sul JY, Kim T et al. 2006. v-ATPase V₀ subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation. Nat. Med. 12:1403–9
    [Google Scholar]
58. 58. 

    Furuya M, Kikuta J, Fujimori S, Seno S, Maeda H et al. 2018. Direct cell-cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo. Nat. Commun. 9:300
    [Google Scholar]
59. 59. 

    Tonna S, Takyar FM, Vrahnas C, Crimeen-Irwin B, Ho PW et al. 2014. EphrinB2 signaling in osteoblasts promotes bone mineralization by preventing apoptosis. FASEB J 28:4482–96
    [Google Scholar]
60. 60. 

    Allan EH, Hausler KD, Wei T, Gooi JH, Quinn JM et al. 2008. EphrinB2 regulation by PTH and PTHrP revealed by molecular profiling in differentiating osteoblasts. J. Bone Miner. Res. 23:1170–81
    [Google Scholar]
61. 61. 

    Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T et al. 2006. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab 4:111–21
    [Google Scholar]
62. 62. 

    Vrahnas C, Blank M, Dite TA, Tatarczuch L, Ansari N et al. 2019. Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone. Nat. Commun. 10:3436
    [Google Scholar]
63. 63. 

    Gerber I, ap Gwynn I 2001. Influence of cell isolation, cell culture density, and cell nutrition on differentiation of rat calvarial osteoblast-like cells in vitro. Eur. Cell Mater. 2:10–20
    [Google Scholar]
64. 64. 

    Ecarot-Charrier B, Glorieux FH, van der Rest M, Pereira G 1983. Osteoblasts isolated from mouse calvaria initiate matrix mineralization in culture. J. Cell Biol. 96:639–43
    [Google Scholar]
65. 65. 

    Negishi-Koga T, Shinohara M, Komatsu N, Bito H, Kodama T et al. 2011. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nat. Med. 17:1473–80
    [Google Scholar]
66. 66. 

    Zhang Y, Wei L, Miron RJ, Shi B, Bian Z 2016. Bone scaffolds loaded with siRNA-Semaphorin4d for the treatment of osteoporosis related bone defects. Sci. Rep. 6:26925
    [Google Scholar]
67. 67. 

    Conrotto P, Valdembri D, Corso S, Serini G, Tamagnone L et al. 2005. Sema4D induces angiogenesis through Met recruitment by Plexin B1. Blood 105:4321–29
    [Google Scholar]
68. 68. 

    Wang X, Kumanogoh A, Watanabe C, Shi W, Yoshida K, Kikutani H 2001. Functional soluble CD100/Sema4D released from activated lymphocytes: possible role in normal and pathologic immune responses. Blood 97:3498–504
    [Google Scholar]
69. 69. 

    Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ 1999. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr. Rev. 20:345–57
    [Google Scholar]
70. 70. 

    Furuya Y, Inagaki A, Khan M, Mori K, Penninger JM et al. 2013. Stimulation of bone formation in cortical bone of mice treated with a receptor activator of nuclear factor-κB ligand (RANKL)-binding peptide that possesses osteoclastogenesis inhibitory activity. J. Biol. Chem. 288:5562–71
    [Google Scholar]
71. 71. 

    Kato G, Shimizu Y, Arai Y, Suzuki N, Sugamori Y et al. 2015. The inhibitory effects of a RANKL-binding peptide on articular and periarticular bone loss in a murine model of collagen-induced arthritis: a bone histomorphometric study. Arthritis Res. Ther. 17:251
    [Google Scholar]
72. 72. 

    Van der Pol E, Boing AN, Harrison P, Sturk A, Nieuwland R 2012. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol. Rev. 64:676–705
    [Google Scholar]
73. 73. 

    Ekström K, Omar O, Graneli C, Wang X, Vazirisani F, Thomsen P 2013. Monocyte exosomes stimulate the osteogenic gene expression of mesenchymal stem cells. PLOS ONE 8:e75227
    [Google Scholar]
74. 74. 

    Huynh N, VonMoss L, Smith D, Rahman I, Felemban MF et al. 2016. Characterization of regulatory extracellular vesicles from osteoclasts. J. Dent. Res. 95:673–79
    [Google Scholar]
75. 75. 

    Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y et al. 2018. Coupling of bone resorption and formation by RANKL reverse signalling. Nature 561:195–200
    [Google Scholar]
76. 76. 

    Lian JB, Stein GS, van Wijnen AJ, Stein JL, Hassan MQ et al. 2012. MicroRNA control of bone formation and homeostasis. Nat. Rev. Endocrinol. 8:212–27
    [Google Scholar]
77. 77. 

    Sun W, Zhao C, Li Y, Wang L, Nie G et al. 2016. Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity. Cell Discov 2:16015
    [Google Scholar]
78. 78. 

    Li D, Liu J, Guo B, Liang C, Dang L et al. 2016. Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat. Commun. 7:10872
    [Google Scholar]
79. 79. 

    Irie N, Takada Y, Watanabe Y, Matsuzaki Y, Naruse C et al. 2009. Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. J. Biol. Chem. 284:14637–44
    [Google Scholar]
80. 80. 

    Zhao C, Sun W, Zhang P, Ling S, Li Y et al. 2015. miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway. RNA Biol 12:343–53
    [Google Scholar]
81. 81. 

    Gray C, Boyde A, Jones SJ 1996. Topographically induced bone formation in vitro: implications for bone implants and bone grafts. Bone 18:115–23
    [Google Scholar]
82. 82. 

    Tonna S, Sims NA. 2014. Talking among ourselves: paracrine control of bone formation within the osteoblast lineage. Calcif. Tissue Int. 94:35–45
    [Google Scholar]
83. 83. 

    Buenzli PR, Sims NA. 2015. Quantifying the osteocyte network in the human skeleton. Bone 75:144–50
    [Google Scholar]
84. 84. 

    McNamara LM, Van der Linden JC, Weinans H, Prendergast PJ 2006. Stress-concentrating effect of resorption lacunae in trabecular bone. J. Biomech. 39:734–41
    [Google Scholar]
85. 85. 

    Rodan GA. 1991. Mechanical loading, estrogen deficiency, and the coupling of bone formation to bone resorption. J. Bone Miner. Res. 6:527–30
    [Google Scholar]
86. 86. 

    Ansari N, Ho PW, Crimeen-Irwin B, Poulton IJ, Brunt AR et al. 2018. Autocrine and paracrine regulation of the murine skeleton by osteocyte-derived parathyroid hormone-related protein. J. Bone Miner. Res. 33:137–53
    [Google Scholar]
87. 87. 

    Rasmussen H, Bordier P. 1974. The Physiological Basis of Metabolic Bone Disease Baltimore: Williams & Wilkins/Waverley Press
88. 88. 

    Kristensen HB, Andersen TL, Marcussen N, Rolighed L, Delaisse JM 2013. Increased presence of capillaries next to remodeling sites in adult human cancellous bone. J. Bone Miner. Res. 28:574–85
    [Google Scholar]
89. 89. 

    Mizoguchi T, Muto A, Udagawa N, Arai A, Yamashita T et al. 2009. Identification of cell cycle-arrested quiescent osteoclast precursors in vivo. J. Cell Biol. 184:541–54
    [Google Scholar]
90. 90. 

    Eghbali-Fatourechi GZ, Modder UI, Charatcharoenwitthaya N, Sanyal A, Undale AH et al. 2007. Characterization of circulating osteoblast lineage cells in humans. Bone 40:1370–77
    [Google Scholar]
91. 91. 

    Jensen PR, Andersen TL, Pennypacker BL, Duong LT, Engelholm LH, Delaisse JM 2014. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently. Biochem. Biophys. Res. Commun. 443:694–99
    [Google Scholar]
92. 92. 

    Narimatsu K, Li M, de Freitas PH, Sultana S, Ubaidus S et al. 2010. Ultrastructural observation on cells meeting the histological criteria for preosteoblasts—a study in the mouse tibial metaphysis. J. Electron Microsc. 59:427–36
    [Google Scholar]
93. 93. 

    Chang MK, Raggatt LJ, Alexander KA, Kuliwaba JS, Fazzalari NL et al. 2008. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J. Immunol. 181:1232–44
    [Google Scholar]
94. 94. 

    Andersen TL, Hauge EM, Rolighed L, Bollerslev J, Kjaersgaard-Andersen P, Delaissé JM 2014. Correlation between absence of bone remodeling compartment canopies, reversal phase arrest, and deficient bone formation in post-menopausal osteoporosis. Am. J. Pathol. 184:1142–51
    [Google Scholar]
95. 95. 

    Jensen PR, Andersen TL, Hauge E-M, Bollerslev J, Delaissé J-M 2015. A joined role of canopy and reversal cells in bone remodeling—lessons from glucocorticoid-induced osteoporosis. Bone 73:16–23
    [Google Scholar]
96. 96. 

    Sayilekshmy M, Hansen RB, Delaissé JM, Rolighed L, Andersen TL, Heegaard AM 2019. Innervation is higher above bone remodeling surfaces and in cortical pores in human bone: lessons from patients with primary hyperparathyroidism. Sci. Rep. 9:5361
    [Google Scholar]
97. 97. 

    Delaissé JM. 2014. The reversal phase of the bone-remodeling cycle: cellular prerequisites for coupling resorption and formation. BoneKEy Rep 3:561
    [Google Scholar]
98. 98. 

    Villanueva AR, Sypitkowski C, Parfitt AM 1986. A new method for identification of cement lines in undecalcified, plastic embedded sections of bone. Stain Technol 61:83–88
    [Google Scholar]
99. 99. 

    Everts V, Delaissé JM, Korper W, Jansen DC, Tigchelaar-Gutter W et al. 2002. The bone lining cell: its role in cleaning Howship's lacunae and initiating bone formation. J. Bone Miner. Res. 17:77–90
    [Google Scholar]
100. 100. 

     Kim SW, Pajevic PD, Selig M, Barry KJ, Yang JY et al. 2012. Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts. J. Bone Miner. Res. 27:2075–84
     [Google Scholar]
101. 101. 

     Abdelgawad ME, Delaissé JM, Hinge M, Jensen PR, Alnaimi RW et al. 2016. Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts. Histochem. Cell Biol. 145:603–15
     [Google Scholar]
102. 102. 

     Lassen NE, Andersen TL, Ploen GG, Soe K, Hauge EM et al. 2017. Coupling of bone resorption and formation in real time: new knowledge gained from human Haversian BMUs. J. Bone Miner. Res. 32:1395–405
     [Google Scholar]
103. 103. 

     Centrella M, Canalis E. 1985. Local regulators of skeletal growth: a perspective. Endocrine Rev 6:544–51
     [Google Scholar]
104. 104. 

     Canalis E, Gabbitas B. 1994. Bone morphogenetic protein 2 increases insulin-like growth factor I and II transcripts and polypeptide levels in bone cell cultures. J. Bone Miner. Res. 9:1999–2005
     [Google Scholar]
105. 105. 

     Fournier T, Riches DW, Winston BW, Rose DM, Young SK et al. 1995. Divergence in macrophage insulin-like growth factor-I (IGF-I) synthesis induced by TNF-alpha and prostaglandin E2. J. Immunol. 155:2123–33
     [Google Scholar]
106. 106. 

     Wang Y, Nishida S, Elalieh HZ, Long RK, Halloran BP, Bikle DD 2006. Role of IGF-I signaling in regulating osteoclastogenesis. J. Bone Miner. Res. 21:1350–58
     [Google Scholar]
107. 107. 

     Kreja L, Brenner RE, Tautzenberger A, Liedert A, Friemert B et al. 2010. Non-resorbing osteoclasts induce migration and osteogenic differentiation of mesenchymal stem cells. J. Cell Biochem. 109:347–55
     [Google Scholar]
108. 108. 

     Zhang L, Leeman E, Carnes DC, Graves DT 1991. Human osteoblasts synthesize and respond to platelet-derived growth factor. Am. J. Physiol. Cell Physiol. 261:C348–54
     [Google Scholar]
109. 109. 

     Daniel TO, Fen Z. 1988. Distinct pathways mediate transcriptional regulation of platelet-derived growth factor B/c-sis expression. J. Biol. Chem. 263:19815–20
     [Google Scholar]
110. 110. 

     Lees RL, Sabharwal VK, Heersche JN 2001. Resorptive state and cell size influence intracellular pH regulation in rabbit osteoclasts cultured on collagen-hydroxyapatite films. Bone 28:187–94
     [Google Scholar]
111. 111. 

     Hock JM, Canalis E. 1994. Platelet-derived growth factor enhances bone cell replication, but not differentiated function of osteoblasts. Endocrinology 134:1423–28
     [Google Scholar]
112. 112. 

     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
     [Google Scholar]
113. 113. 

     Mitlak BH, Finkelman RD, Hill EL, Li J, Martin B et al. 1996. The effect of systemically administered PDGF-BB on the rodent skeleton. J. Bone Miner. Res. 11:238–47
     [Google Scholar]
114. 114. 

     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. 158:817–23
     [Google Scholar]
115. 115. 

     Garimella R, Tague SE, Zhang J, Belibi F, Nahar N et al. 2008. Expression and synthesis of bone morphogenetic proteins by osteoclasts: a possible path to anabolic bone remodeling. J. Histochem. Cytochem. 56:569–77
     [Google Scholar]
116. 116. 

     Robubi A, Berger C, Schmid M, Huber KR, Engel A, Krugluger W 2014. Gene expression profiles induced by growth factors in in vitro cultured osteoblasts. Bone Joint Res 3:236–40
     [Google Scholar]
117. 117. 

     Champagne CM, Takebe J, Offenbacher S, Cooper LF 2002. Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. Bone 30:26–31
     [Google Scholar]
118. 118. 

     Fiedler J, Röderer G, Günther KP, Brenner RE 2002. BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. J. Cell. Biochem. 87:305–12
     [Google Scholar]
119. 119. 

     Rickard DJ, Sullivan TA, Shenker BJ, Leboy PS, Kazhdan I 1994. Induction of rapid osteoblast differentiation in rat bone marrow stromal cell cultures by dexamethasone and BMP-2. Dev. Biol. 161:218–28
     [Google Scholar]
120. 120. 

     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. 148:281–90
     [Google Scholar]
121. 121. 

     Robey PG, Young MF, Flanders KC, Roche NS, Kondaiah P et al. 1987. Osteoblasts synthesize and respond to transforming growth factor-type beta (TGF-beta) in vitro. J. Cell Biol. 105:457–63
     [Google Scholar]
122. 122. 

     Chen W, Jin W, Wahl SM 1998. Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces transforming growth factor β (TGF-β) production by murine CD4⁺ T cells. J. Exp. Med. 188:1849–57
     [Google Scholar]
123. 123. 

     Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM 1998. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-β, PGE2, and PAF. J. Clin. Investig. 101:890–98
     [Google Scholar]
124. 124. 

     Hock JM, Canalis E, Centrella M 1990. Transforming growth factor-β stimulates bone matrix apposition and bone cell replication in cultured fetal rat calvariae. Endocrinology 126:421–26
     [Google Scholar]
125. 125. 

     Galvin RJS, Gatlin CL, Horn JW, Fuson TR 1999. TGF-β enhances osteoclast differentiation in hematopoietic cell cultures stimulated with RANKL and M-CSF. Biochem. Biophys. Res. Commun. 265:233–39
     [Google Scholar]
126. 126. 

     Loots GG, Keller H, Leupin O, Murugesh D, Collette NM, Genetos DC 2012. TGF-β regulates sclerostin expression via the ECR5 enhancer. Bone 50:663–69
     [Google Scholar]
127. 127. 

     Friedman MS, Long MW, Hankenson KD 2006. Osteogenic differentiation of human mesenchymal stem cells is regulated by bone morphogenetic protein-6. J. Cell. Biochem. 98:538–54
     [Google Scholar]
128. 128. 

     Wutzl A, Brozek W, Lernbass I, Rauner M, Hofbauer G et al. 2006. Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation. J. Biomed. Mater. Res. A 77:75–83
     [Google Scholar]
129. 129. 

     Terauchi M, Li JY, Bedi B, Baek KH, Tawfeek H et al. 2009. T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling. Cell Metab 10:229–40
     [Google Scholar]
130. 130. 

     Bennett CN, Ouyang H, Ma YL, Zeng Q, Gerin I et al. 2007. Wnt10b increases postnatal bone formation by enhancing osteoblast differentiation. J. Bone Miner. Res. 22:1924–32
     [Google Scholar]
131. 131. 

     Scariano JK, Emery-Cohen AJ, Pickett GG, Morgan M, Simons PC, Alba F 2008. Estrogen receptors alpha (ESR1) and beta (ESR2) are expressed in circulating human lymphocytes. J. Recept. Signal Transduct. Res. 28:285–93
     [Google Scholar]
132. 132. 

     Pappu R, Schwab SR, Cornelissen I, Pereira JP, Regard JB et al. 2007. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316:295–98
     [Google Scholar]
133. 133. 

     Jin YR, Stohn JP, Wang Q, Nagano K, Baron R et al. 2017. Inhibition of osteoclast differentiation and collagen antibody-induced arthritis by CTHRC1. Bone 97:153–67
     [Google Scholar]
134. 134. 

     Matsuoka K, Park KA, Ito M, Ikeda K, Takeshita S 2014. Osteoclast-derived complement component 3a stimulates osteoblast differentiation. J. Bone Miner. Res. 29:1522–30
     [Google Scholar]
135. 135. 

     Wlazlo N, van Greevenbroek MM, Ferreira I, Jansen EH, Feskens EJ et al. 2013. Activated complement factor 3 is associated with liver fat and liver enzymes: the CODAM study. Eur. J. Clin. Investig. 43:679–88
     [Google Scholar]
136. 136. 

     Sato T, Abe E, Jin CH, Hong MH, Katagiri T et al. 1993. The biological roles of the third component of complement in osteoclast formation. Endocrinology 133:397–404
     [Google Scholar]
137. 137. 

     Fernandes TJ, Hodge JM, Singh PP, Eeles DG, Collier FM et al. 2013. Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner. PLOS ONE 8:e73266
     [Google Scholar]
138. 138. 

     Zarling JM, Shoyab M, Marquardt H, Hanson MB, Lioubin MN, Todaro GJ 1986. Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. PNAS 83:9739–43
     [Google Scholar]
139. 139. 

     Clegg CH, Rulffes JT, Wallace PM, Haugen HS 1996. Regulation of an extrathymic T-cell development pathway by oncostatin M. Nature 384:261–63
     [Google Scholar]
140. 140. 

     Tamura T, Udagawa N, Takahashi N, Miyaura C, Tanaka S et al. 1993. Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. PNAS 90:11924–28
     [Google Scholar]
141. 141. 

     Ota K, Quint P, Weivoda MM, Ruan M, Pederson L et al. 2013. Transforming growth factor beta 1 induces CXCL16 and leukemia inhibitory factor expression in osteoclasts to modulate migration of osteoblast progenitors. Bone 57:68–75
     [Google Scholar]
142. 142. 

     Wågsäter D, Olofsson PS, Norgren L, Stenberg B, Sirsjö A 2004. The chemokine and scavenger receptor CXCL16/SR-PSOX is expressed in human vascular smooth muscle cells and is induced by interferon γ. Biochem. Biophys. Res. Commun. 325:1187–93
     [Google Scholar]
143. 143. 

     Barlic J, Zhu W, Murphy PM 2009. Atherogenic lipids induce high-density lipoprotein uptake and cholesterol efflux in human macrophages by up-regulating transmembrane chemokine CXCL16 without engaging CXCL16-dependent cell adhesion. J. Immunol. 182:7928–36
     [Google Scholar]
144. 144. 

     Whitney MJ, Lee A, Ylostalo J, Zeitouni S, Tucker A, Gregory CA 2009. Leukemia inhibitory factor secretion is a predictor and indicator of early progenitor status in adult bone marrow stromal cells. Tissue Eng. A 15:33–44
     [Google Scholar]
145. 145. 

     Cornish J, Callon K, King A, Edgar S, Reid IR 1993. The effect of leukemia inhibitory factor on bone in vivo. Endocrinology 132:1359–66
     [Google Scholar]
146. 146. 

     Cornish J, Callon KE, Edgar SG, Reid IR 1997. Leukemia inhibitory factor is mitogenic to osteoblasts. Bone 21:243–47
     [Google Scholar]
147. 147. 

     Poulton IJ, McGregor NE, Pompolo S, Walker EC, Sims NA 2012. Contrasting roles of leukemia inhibitory factor in murine bone development and remodeling involve region-specific changes in vascularization. J. Bone Miner. Res. 27:586–95
     [Google Scholar]
148. 148. 

     Reid LR, Lowe C, Cornish J, Skinner SJ, Hilton DJ et al. 1990. Leukemia inhibitory factor: a novel bone-active cytokine. Endocrinology 126:1416–20
     [Google Scholar]
149. 149. 

     Kim BJ, Lee YS, Lee SY, Baek WY, Choi YJ et al. 2018. Osteoclast-secreted SLIT3 coordinates bone resorption and formation. J. Clin. Investig. 128:1429–41
     [Google Scholar]
150. 150. 

     Xu R, Yallowitz A, Qin A, Wu Z, Shin DY et al. 2018. Targeting skeletal endothelium to ameliorate bone loss. Nat. Med. 24:823–33
     [Google Scholar]
151. 151. 

     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
     [Google Scholar]
152. 152. 

     Takyar FM, Tonna S, Ho PW, Crimeen-Irwin B, Baker EK et al. 2013. EphrinB2/EphB4 inhibition in the osteoblast lineage modifies the anabolic response to parathyroid hormone. J. Bone Miner. Res. 28:912–25
     [Google Scholar]
153. 153. 

     Kartsogiannis V, Zhou H, Horwood NJ, Thomas RJ, Hards DK et al. 1999. Localization of RANKL (receptor activator of NFκB ligand) mRNA and protein in skeletal and extraskeletal tissues. Bone 25:525–34
     [Google Scholar]