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The Role of GPR55 in Bone Biology

  • Lauren S. Whyte
  • Ruth A. Ross
Chapter
Part of the The Receptors book series (REC, volume 24)

Abstract

A novel and necessary role for GPR55 in bone physiology was demonstrated by Whyte et al. (Proc Natl Acad Sci 106(38):16551–16516, 2009). This chapter aims to summarise the work that became the first study to demonstrate a non-neuronal physiological role for GPR55 in vivo. In summary, male mice lacking GPR55 develop a high bone mass phenotype due to impairment in osteoclast function—consistent with GPR55 agonists O-1602 and LPI stimulating osteoclast function. These studies advocate the development of GPR55 antagonists for the treatment of diseases associated with excessive osteoclast activity such as osteoporosis.

Keywords

Osteoclast Differentiation Osteoclast Formation Osteoclast Function Osteoclast Resorption Bone Phenotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Alliston T, Derynck R (2002) Medicine: interfering with bone remodelling. Nature 416:686–687. doi: 10.1038/416686a PubMedCrossRefGoogle Scholar
  2. Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER et al (1997) A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390:175–179. doi: 10.1038/36593 PubMedCrossRefGoogle Scholar
  3. Arron JR, Choi Y (2000) Osteoimmunology: bone versus immune system. Nature 408:535–536PubMedCrossRefGoogle Scholar
  4. Baker D, Pryce G, Davies WL, Hiley CR (2006) In silico patent searching reveals a new cannabinoid receptor. Trends Pharmacol Sci 27:1–4. doi: 10.1016/j.tips.2005.11.003 PubMedCrossRefGoogle Scholar
  5. Begg M, Pacher P, Batkai S, Osei-Hyiaman D, Offertaler L, Mo FM et al (2005) Evidence for novel cannabinoid receptors. [review] [116 refs]. Pharmacol Ther 106:133–145PubMedCrossRefGoogle Scholar
  6. Besbas N, Draaken M, Ludwig M, Deren O, Orhan D, Bilginer Y et al (2009) A novel CLCN7 mutation resulting in a most severe form of autosomal recessive osteopetrosis. Eur J Pediatr 168(12):1449–1454. doi: 10.1007/s00431-009-0945-9 PubMedCrossRefGoogle Scholar
  7. Bilezikian J (2008) Combination anabolic and antiresorptive therapy for osteoporosis: opening the anabolic window. Curr Osteoporos Rep 6:24–30PubMedCrossRefGoogle Scholar
  8. Blair HC (1998) How the osteoclast degrades bone. Bioessays 20:837–846PubMedCrossRefGoogle Scholar
  9. Blair HC, Kahn AJ, Crouch EC, Jeffrey JJ, Teitelbaum SL (1986) Isolated osteoclasts resorb the organic and inorganic components of bone. J Cell Biol 102:1164–1172PubMedCrossRefGoogle Scholar
  10. Bondarenko A, Waldeck-Weiermair M, Naghdi S, Poteser M, Malli R, Graier WF (2010) GPR55-dependent and -independent ion signaling in response to lysophosphatidylinositol in endothelial cells. Br J Pharmacol 161:308–320. doi: 10.1111/j.1476-5381.2010.00744.x PubMedCrossRefGoogle Scholar
  11. Boonen S, Vanderschueren D, Venken K, Milisen K, Delforge M, Haentjens P (2008) Recent developments in the management of postmenopausal osteoporosis with bisphosphonates: enhanced efficacy by enhanced compliance. J Intern Med 264:315–332. doi: 10.1111/j.1365-2796.2008.02010.x PubMedCrossRefGoogle Scholar
  12. Borthwick KJ, Kandemir N, Topaloglu R, Kornak U, Bakkaloglu A, Yordam N et al (2003) A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis. J Med Genet 40:115–121PubMedCrossRefGoogle Scholar
  13. Bosier B, Hermans E (2007) Versatility of GPCR recognition by drugs: from biological implications to therapeutic relevance. Trends Pharmacol Sci 28:438–446PubMedCrossRefGoogle Scholar
  14. Brennan TC, Rybchyn MS, Green W, Atwa S, Conigrave AD, Mason RS (2009) Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol 157:1291–1300. doi: 10.1111/j.1476-5381.2009.00305.x PubMedCrossRefGoogle Scholar
  15. Brown AJ (2007) Novel cannabinoid receptors. Br J Pharmacol 152:567–575. doi: 10.1038/sj.bjp.0707481 PubMedCrossRefGoogle Scholar
  16. Busch L, Sterin-Borda L, Borda E (2006) Effects of castration on cannabinoid CB1 receptor expression and on the biological actions of cannabinoid in the parotid gland. Clin Exp Pharmacol Physiol 33:258–263PubMedCrossRefGoogle Scholar
  17. Chan GK, Miao D, Deckelbaum R, Bolivar I, Karaplis A, Goltzman D (2003) Parathyroid ­hormone-related peptide interacts with bone morphogenetic protein 2 to increase osteoblastogenesis and decrease adipogenesis in pluripotent C3H10T 1/2 mesenchymal cells. Endocrinology 144:5511–5520. doi: 10.1210/en.2003-0273 PubMedCrossRefGoogle Scholar
  18. Chellaiah MA (2005) Regulation of actin ring formation by rho GTPases in osteoclasts. J Biol Chem 280:32930–32943PubMedCrossRefGoogle Scholar
  19. Chellaiah MA (2006) Regulation of podosomes by integrin alphavbeta3 and Rho GTPase-facilitated phosphoinositide signaling. Eur J Cell Biol 85:311–317PubMedCrossRefGoogle Scholar
  20. Chellaiah MA, Soga N, Swanson S, McAllister S, Alvarez U, Wang D et al (2000) Rho-A is critical for osteoclast podosome organization, motility, and bone resorption. J Biol Chem 275:11993–12002PubMedCrossRefGoogle Scholar
  21. Clines GA, Guise TA (2008) Molecular mechanisms and treatment of bone metastasis. Expert Rev Mol Med 10:e7. doi: 10.1017/S1462399408000616 PubMedCrossRefGoogle Scholar
  22. Compston JE (2001) Sex steroids and bone. Physiol Rev 81:419–447PubMedGoogle Scholar
  23. Compston J (2009) Clinical and therapeutic aspects of osteoporosis. Eur J Radiol 71(3):388–391. doi: 10.1016/j.ejrad.2008.04.063 PubMedCrossRefGoogle Scholar
  24. Cooper MS (2009) The system of 11β-hydroxysteroid dehydrogenases: relevance to inflammatory bone loss. Bone 45:S123. doi: 10.1016/j.bone.2009.07.026 CrossRefGoogle Scholar
  25. Cowin SC, Moss-Salentijn L, Moss ML (1991) Candidates for the mechanosensory system in bone. J Biomech Eng 113:191–197PubMedCrossRefGoogle Scholar
  26. Coxon FP, Thompson K, Rogers MJ (2006) Recent advances in understanding the mechanism of action of bisphosphonates. Curr Opin Pharmacol 6:307–312. doi: 10.1016/j.coph.2006.03.005 PubMedCrossRefGoogle Scholar
  27. De Leenheer E, Mueller GS, Vanderkerken K, Croucher PI (2004) Evidence of a role for RANKL in the development of myeloma bone disease. Curr Opin Pharmacol 4:340–346. doi: 10.1016/j.coph.2004.03.011 PubMedCrossRefGoogle Scholar
  28. Del Fattore A, Fornari R, Van Wesenbeeck L, de Freitas F, Timmermans JP, Peruzzi B et al (2008a) A new heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin homolog domain containing family M (with run domain) member 1 (PLEKHM1), impairs vesicular acidification and increases TRACP secretion in osteoclasts. J Bone Miner Res 23:380–391. doi: 10.1359/jbmr.071107 PubMedCrossRefGoogle Scholar
  29. Del Fattore A, Teti A, Rucci N (2008b) Osteoclast receptors and signaling. Arch Biochem Biophys 473:147–160. doi: 10.1016/j.abb.2008.01.011 PubMedCrossRefGoogle Scholar
  30. Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z et al (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410:822–825. doi: 10.1038/35071088 PubMedCrossRefGoogle Scholar
  31. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T et al (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424PubMedCrossRefGoogle Scholar
  32. Dubrow SA, Hruby PM, Akhter MP (2007) Gender specific LRP5 influences on trabecular bone structure and strength. J Musculoskelet Neuronal Interact 7:166–173PubMedGoogle Scholar
  33. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT et al (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207PubMedCrossRefGoogle Scholar
  34. Duong LT, Lakkakorpi P, Nakamura I, Rodan GA (2000) Integrins and signaling in osteoclast function. Matrix Biol 19:97–105PubMedCrossRefGoogle Scholar
  35. Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X et al (2005) Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434:514–520. doi: 10.1038/nature03398 PubMedCrossRefGoogle Scholar
  36. Epstein S (2006) Update of current therapeutic options for the treatment of postmenopausal osteoporosis. Clin Ther 28:151–173. doi: 10.1016/j.clinthera.2006.02.007 PubMedCrossRefGoogle Scholar
  37. Falasca M, Corda D (1994) Elevated levels and mitogenic activity of lysophosphatidylinositol in k-ras-transformed epithelial cells. Eur J Biochem 221:383–389PubMedCrossRefGoogle Scholar
  38. Feldkamp LA, Goldstein SA, Parfitt AM, Jesion G, Kleerekoper M (1989) The direct examination of three-dimensional bone architecture in vitro by computed tomography. J Bone Miner Res 4:3–11PubMedCrossRefGoogle Scholar
  39. Fisher JE, Caulfield MP, Sato M, Quartuccio HA, Gould RJ, Garsky VM et al (1993) Inhibition of osteoclastic bone resorption in vivo by echistatin, an “arginyl-glycyl-aspartyl” (RGD)-containing protein. Endocrinology 132:1411–1413PubMedCrossRefGoogle Scholar
  40. Ford LA, Roelofs AJ, Anavi-Goffer S, Mowat L, Simpson DG, Irving AJ et al (2010) A role for L-alpha-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells. Br J Pharmacol 160:762–771. doi: 10.1111/j.1476-5381.2010.00743.x PubMedCrossRefGoogle Scholar
  41. Gallagher JC (2008) Advances in bone biology and new treatments for bone loss. Maturitas 60:65–69. doi: 10.1016/j.maturitas.2008.04.005 PubMedCrossRefGoogle Scholar
  42. Gao Y, Grassi F, Ryan MR, Terauchi M, Page K, Yang X et al (2007) IFN-γ stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. J Clin Invest 117:122–132PubMedCrossRefGoogle Scholar
  43. Gianni W, Ricci A, Gazzaniga P, Brama M, Pietropaolo M, Votano S et al (2004) Raloxifene modulates interleukin-6 and tumor necrosis factor-{alpha} synthesis in vivo: results from a Pilot Clinical Study. J Clin Endocrinol Metab 89:6097–6099. doi: 10.1210/jc.2004-0795 PubMedCrossRefGoogle Scholar
  44. Gingery A, Bradley E, Shaw A, Oursler MJ (2003) Phosphatidylinositol 3-kinase coordinately activates the MEK/ERK and AKT/NFkappaB pathways to maintain osteoclast survival. J Cell Biochem 89:165–179. doi: 10.1002/jcb.10503 PubMedCrossRefGoogle Scholar
  45. Glass DA II, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H et al (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764. doi: 10.1016/j.devcel.2005.02.017 PubMedCrossRefGoogle Scholar
  46. Gowen M, Stroup GB, Dodds RA, James IE, Votta BJ, Smith BR et al (2000) Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest 105:1595–1604PubMedCrossRefGoogle Scholar
  47. Grey A (2007) Emerging pharmacologic therapies for osteoporosis. Expert Opin Emerg Drugs 12:493–508PubMedCrossRefGoogle Scholar
  48. Guerrini MM, Sobacchi C, Cassani B, Abinun M, Kilic SS, Pangrazio A et al (2008) Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. Am J Hum Genet 83:64–76. doi: 10.1016/j.ajhg.2008.06.015 PubMedCrossRefGoogle Scholar
  49. Guimarães VMC, Zuardi AW, Del Bel EA, Guimarães FS (2004) Cannabidiol increases Fos expression in the nucleus accumbens but not in the dorsal striatum. Life Sci 75:633–638PubMedCrossRefGoogle Scholar
  50. Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG et al (1998) Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13. Science 280:2112–2114PubMedCrossRefGoogle Scholar
  51. Helfrich MH, Hocking LJ (2008) Genetics and aetiology of Pagetic disorders of bone. Arch Biochem Biophys 473:172–182. doi: 10.1016/j.abb.2008.02.045 PubMedCrossRefGoogle Scholar
  52. Helfrich MH, Nesbitt SA, Dorey EL, Horton MA (1992) Rat osteoclasts adhere to a wide range of RGD (Arg-Gly-Asp) peptide-containing proteins, including the bone sialoproteins and fibronectin, via a beta 3 integrin. J Bone Miner Res 7:335–343PubMedCrossRefGoogle Scholar
  53. Helfrich MH, Nesbitt SA, Lakkakorpi PT, Barnes MJ, Bodary SC, Shankar G et al (1996) β1 integrins and osteoclast function: involvement in collagen recognition and bone resorption. Bone 19:317–328. doi: 10.1016/S8756-3282(96)00223-2 PubMedCrossRefGoogle Scholar
  54. Helms WS, Jeffrey JL, Holmes DA, Townsend MB, Clipstone NA, Su L (2007) Modulation of NFAT-dependent gene expression by the RhoA signaling pathway in T cells. J Leukoc Biol 82:361–369. doi: 10.1189/jlb.0206120 PubMedCrossRefGoogle Scholar
  55. Henstridge CM, Balenga NA, Ford LA, Ross RA, Waldhoer M, Irving AJ (2009) The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation. FASEB J 23:183–193. doi: 10.1096/fj.08-108670 PubMedCrossRefGoogle Scholar
  56. Henstridge CM, Balenga NA, Kargl J, Andradas C, Brown AJ, Irving A et al (2011) Minireview: recent developments in the physiology and pathology of the lysophosphatidylinositol-sensitive receptor GPR55. Mol Endocrinol 25:1835–1848. doi: 10.1210/me.2011-1197 PubMedCrossRefGoogle Scholar
  57. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 11:563–583PubMedGoogle Scholar
  58. Hoeppner LH, Secreto FJ, Westendorf JJ (2009) Wnt signaling as a therapeutic target for bone diseases. Expert Opin Ther Targets 13:485–496PubMedCrossRefGoogle Scholar
  59. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL (1999) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140:4367–4370PubMedCrossRefGoogle Scholar
  60. Idris AI, van’t Hof RJ, Greig IR, Ridge SA, Baker D, Ross RA et al (2005) Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat Med 11:774–779PubMedCrossRefGoogle Scholar
  61. Idris AI, Sophocleous A, Landao-Bassonga E, van’t Hof RJ, Ralston SH (2008) Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss by the type 2 cannabinoid receptor. Endocrinology 149:5619–5626. doi: 10.1210/en.2008-0150 PubMedCrossRefGoogle Scholar
  62. Ishiguro H, Onaivi ES, Horiuchi Y, Imai K, Komaki G, Ishikawa T et al (2011) Functional polymorphism in the GPR55 gene is associated with anorexia nervosa. Synapse 65:103–108. doi: 10.1002/syn.20821;10.1002/syn.20821 PubMedCrossRefGoogle Scholar
  63. Ito M (2005) Assessment of bone quality using micro-computed tomography (micro-CT) and synchrotron micro-CT. J Bone Miner Metab 23(suppl):115–121PubMedCrossRefGoogle Scholar
  64. Jarai Z, Wagner JA, Varga K, Lake KD, Compton DR, Martin BR et al (1999) Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc Natl Acad Sci U S A 96:14136–14141PubMedCrossRefGoogle Scholar
  65. Jiang Y, Zhao J, Liao EY, Dai RC, Wu XP, Genant HK (2005) Application of micro-CT assessment of 3-D bone microstructure in preclinical and clinical studies. J Bone Miner Metab 23(suppl):122–131PubMedCrossRefGoogle Scholar
  66. Jiang Y, Jacobson J, Genant HK, Zhao J (2007) Application of micro-CT and MRI in clinical and preclinical studies of osteoporosis and related disorders. In: Qin L, Genant HK, Griffith J, Leung K-S (eds) Advanced bioimaging technologies in assessment of the quality of bone and scaffold materials. Springer, Heidelberg, pp 399–415CrossRefGoogle Scholar
  67. Johns DG, Behm DJ, Walker DJ, Ao Z, Shapland EM, Daniels DA et al (2007) The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Br J Pharmacol 152:825–831. doi: 10.1038/sj.bjp.0707419 PubMedCrossRefGoogle Scholar
  68. Joost P, Methner A (2002) Phylogenetic analysis of 277 human G-protein-coupled receptors as a tool for the prediction of orphan receptor ligands. Genome Biol 3:RESEARH0063CrossRefGoogle Scholar
  69. Kapur A, Zhao P, Sharir H, Bai Y, Caron MG, Barak LS et al (2009) Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands. J Biol Chem 284:29817–29827. doi: 10.1074/jbc.M109.050187 PubMedCrossRefGoogle Scholar
  70. Kargl J, Balenga N, Platzer W, Martini L, Whistler J, Waldhoer M (2012) The GPCR-associated sorting protein 1 regulates ligand-induced downregulation of GPR55. Br J Pharmacol 165(8):2611–2619. doi: 10.1111/j.1476-5381.2011.01562.x;10.1111/j.1476-5381.2011.01562.x PubMedCrossRefGoogle Scholar
  71. Karsak M, Cohen-Solal M, Freudenberg J, Ostertag A, Morieux C, Kornak U et al (2005) Cannabinoid receptor type 2 gene is associated with human osteoporosis. Hum Mol Genet 14:3389–3396PubMedCrossRefGoogle Scholar
  72. Klein-Nulend J, Semeins CM, Ajubi NE, Nijweide PJ, Burger EH (1995) Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts—correlation with prostaglandin upregulation. Biochem Biophys Res Commun 217:640–648PubMedCrossRefGoogle Scholar
  73. Kong Y, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S et al (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402:304–309PubMedCrossRefGoogle Scholar
  74. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMedCrossRefGoogle Scholar
  75. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A 105:2699–2704. doi: 10.1073/pnas.0711278105 PubMedCrossRefGoogle Scholar
  76. Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552–3561PubMedCrossRefGoogle Scholar
  77. Lee SE, Chung WJ, Kwak HB, Chung CH, Kwack KB, Lee ZH et al (2001) Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK. J Biol Chem 276:49343–49349. doi: 10.1074/jbc.M103642200 PubMedCrossRefGoogle Scholar
  78. Lewiecki EM (2009) Denosumab update. Curr Opin Rheumatol 21:369–373. doi: 10.1097/BOR.0b013e32832ca41c PubMedCrossRefGoogle Scholar
  79. Lian JB, Stein GS, Aubin JE (2003) Chapter 3. Bone formation: maturation and functional activities of osteoblast lineage cells. Primer 5:13–28Google Scholar
  80. Luchin A, Purdom G, Murphy K, Clark MY, Angel N, Cassady AI et al (2000) The microphthalmia transcription factor regulates expression of the tartrate-resistant acid phosphatase gene during terminal differentiation of osteoclasts. J Bone Miner Res 15:451–460PubMedCrossRefGoogle Scholar
  81. Mackie K, Stella N (2006) Cannabinoid receptors and endocannabinoids: evidence for new players. AAPS J 8:E298–E306. doi: 10.1208/aapsj080234 PubMedGoogle Scholar
  82. Mailman RB (2007) GPCR functional selectivity has therapeutic impact. Trends Pharmacol Sci 28:390–396. doi: 10.1016/j.tips.2007.06.002 PubMedCrossRefGoogle Scholar
  83. Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andreakos E, Mechoulam R et al (2000) The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci U S A 97:9561–9566. doi: 10.1073/pnas.160105897 PubMedCrossRefGoogle Scholar
  84. Martin TJ, Udagawa N (1998) Hormonal regulation of osteoclast function. Trends Endocrinol Metab 9:6–12PubMedCrossRefGoogle Scholar
  85. McHugh KP, Hodivala-Dilke K, Zheng MH, Namba N, Lam J, Novack D et al (2000) Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts. J Clin Invest 105:433–440. doi: 10.1172/JCI8905 PubMedCrossRefGoogle Scholar
  86. McHugh D, Tanner C, Mechoulam R, Pertwee RG, Ross RA (2008) Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2. Mol Pharmacol 73:441–450. doi: 10.1124/mol.107.041863 PubMedCrossRefGoogle Scholar
  87. McPartland JM, Glass M, Pertwee RG (2007) Meta-analysis of cannabinoid ligand binding affinity and receptor distribution: interspecies differences. Br J Pharmacol 152:583–593PubMedCrossRefGoogle Scholar
  88. Meadows NA, Sharma SM, Faulkner GJ, Ostrowski MC, Hume DA, Cassady AI (2007) The expression of Clcn7 and Ostm1 in osteoclasts is coregulated by microphthalmia transcription factor. J Biol Chem 282:1891–1904. doi: 10.1074/jbc.M608572200 PubMedCrossRefGoogle Scholar
  89. Metz SA (1986) Lysophosphatidylinositol, but not lysophosphatidic acid, stimulates insulin release. A possible role for phospholipase A2 but not de novo synthesis of lysophospholipid in pancreatic islet function. Biochem Biophys Res Commun 138:720–727PubMedCrossRefGoogle Scholar
  90. Miyazaki T, Katagiri H, Kanegae Y, Takayanagi H, Sawada Y, Yamamoto A et al (2000) Reciprocal role of ERK and NF-kappaB pathways in survival and activation of osteoclasts. J Cell Biol 148:333–342PubMedCrossRefGoogle Scholar
  91. Monet M, Gkika D, Lehen’kyi V, Pourtier A, Vanden Abeele F, Bidaux G et al (2009) Lysophospholipids stimulate prostate cancer cell migration via TRPV2 channel activation. Biochim Biophys Acta 1793:528–539. doi: 10.1016/j.bbamcr.2009.01.003 PubMedCrossRefGoogle Scholar
  92. Motyckova G, Weilbaecher KN, Horstmann M, Rieman DJ, Fisher DZ, Fisher DE (2001) Linking osteopetrosis and pycnodysostosis: regulation of cathepsin K expression by the microphthalmia transcription factor family. Proc Natl Acad Sci U S A 98:5798–5803. doi: 10.1073/pnas.091479298 PubMedCrossRefGoogle Scholar
  93. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR et al (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29. doi: 10.1016/S0092-8674(01)00622-5 PubMedCrossRefGoogle Scholar
  94. Napimoga MH, Benatti BB, Lima FO, Alves PM, Campos AC, Pena-Dos-Santos DR et al (2009) Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats. Int Immunopharmacol 9:216–222. doi: 10.1016/j.intimp.2008.11.010 PubMedCrossRefGoogle Scholar
  95. Nefussi JR, Boy-Lefevre ML, Boulekbache H, Forest N (1985) Mineralization in vitro of matrix formed by osteoblasts isolated by collagenase digestion. Differentiation 29:160–168PubMedCrossRefGoogle Scholar
  96. Notarnicola M, Messa C, Orlando A, Bifulco M, Laezza C, Gazzerro P et al (2008) Estrogenic induction of cannabinoid CB1 receptor in human colon cancer cell lines. Scand J Gastroenterol 43:66–72PubMedCrossRefGoogle Scholar
  97. Obara Y, Ueno S, Yanagihata Y, Nakahata N (2011) Lysophosphatidylinositol causes neurite retraction via GPR55, G13 and RhoA in PC12 cells. PLoS One 6:e24284. doi: 10.1371/journal.pone.0024284 PubMedCrossRefGoogle Scholar
  98. Ochotny N, Van Vliet A, Chan N, Yao Y, Morel M, Kartner N et al (2006) Effects of human a3 and a4 mutations that result in osteopetrosis and distal renal tubular acidosis on yeast V-ATPase expression and activity. J Biol Chem 281:26102–26111. doi: 10.1074/jbc.M601118200 PubMedCrossRefGoogle Scholar
  99. Odgren PR, Kim N, MacKay CA, Mason-Savas A, Choi Y, Marks SC Jr (2003) The role of RANKL (TRANCE/TNFSF11), a tumor necrosis factor family member, in skeletal development: effects of gene knockout and transgenic rescue. Connect Tissue Res 44(suppl 1): 264–271PubMedGoogle Scholar
  100. Ofek O, Karsak M, Leclerc N, Fogel M, Frenkel B, Wright K et al (2006) Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci U S A 103:696–701PubMedCrossRefGoogle Scholar
  101. Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T (2007) Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun 362:928–934. doi: 10.1016/j.bbrc.2007.08.078 PubMedCrossRefGoogle Scholar
  102. Oka S, Toshida T, Maruyama K, Nakajima K, Yamashita A, Sugiura T (2009) 2-Arachidonoyl-sn-glycero-3-phosphoinositol: a possible natural ligand for GPR55. J Biochem 145:13–20. doi: 10.1093/jb/mvn136 PubMedCrossRefGoogle Scholar
  103. Oka S, Kimura S, Toshida T, Ota R, Yamashita A, Sugiura T (2010) Lysophosphatidylinositol induces rapid phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2 in HEK293 cells expressing GPR55 and IM-9 lymphoblastoid cells. J Biochem 147:671–678. doi: 10.1093/jb/mvp208 PubMedCrossRefGoogle Scholar
  104. Ornitz DM (2005) FGF signaling in the developing endochondral skeleton. Cytokine Growth Factor Rev 16:205–213. doi: 10.1016/j.cytogfr.2005.02.003 PubMedCrossRefGoogle Scholar
  105. Ory S, Brazier H, Pawlak G, Blangy A (2008) Rho GTPases in osteoclasts: orchestrators of podosome arrangement. Eur J Cell Biol 87:469–477. doi: 10.1016/j.ejcb.2008.03.002 PubMedCrossRefGoogle Scholar
  106. Parfitt AM (2002) Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone 30:5–7. doi: 10.1016/S8756-3282(01)00642-1 PubMedCrossRefGoogle Scholar
  107. Paton WDM, Pertwee RG (1973) The pharmacology of cannabis in animals. In: Mechoulam R (ed) Marijuana: chemistry, pharmacology, metabolism and clinical effects. Academic, New YorkGoogle Scholar
  108. Pertwee RG (2007) GPR55: a new member of the cannabinoid receptor clan? Br J Pharmacol 152:984–986. doi: 10.1038/sj.bjp.0707464 PubMedCrossRefGoogle Scholar
  109. Pineiro R, Maffucci T, Falasca M (2011) The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene 30:142–152. doi: 10.1038/onc.2010.417 PubMedCrossRefGoogle Scholar
  110. Reid IR (2008) Anti-resorptive therapies for osteoporosis. Semin Cell Dev Biol 19:473–478. doi: 10.1016/j.semcdb.2008.08.002 PubMedCrossRefGoogle Scholar
  111. Riggs BL (2000) The mechanisms of estrogen regulation of bone resorption. J Clin Invest 106:1203–1204. doi: 10.1172/JCI11468 PubMedCrossRefGoogle Scholar
  112. Roggia C, Gao Y, Cenci S, Weitzmann MN, Toraldo G, Isaia G et al (2001) Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc Natl Acad Sci U S A 98:13960–13965PubMedCrossRefGoogle Scholar
  113. Romero-Zerbo SY, Rafacho A, Diaz-Arteaga A, Suarez J, Quesada I, Imbernon M et al (2011) A role for the putative cannabinoid receptor GPR55 in the islets of Langerhans. J Endocrinol 211:177–185. doi: 10.1530/JOE-11-0166 PubMedCrossRefGoogle Scholar
  114. Ross FP (2000) RANKing the importance of measles virus in Paget’s disease. J Clin Invest 105:555–558. doi: 10.1172/JCI9557 PubMedCrossRefGoogle Scholar
  115. Ross RA (2009) The enigmatic pharmacology of GPR55. Trends Pharmacol Sci 30:156–163. doi: 10.1016/j.tips.2008.12.004 PubMedCrossRefGoogle Scholar
  116. Ross RA (2011) L-alpha-lysophosphatidylinositol meets GPR55: a deadly relationship. Trends Pharmacol Sci 32:265–269. doi: 10.1016/j.tips.2011.01.005 PubMedCrossRefGoogle Scholar
  117. Rossi F, Siniscalco D, Luongo L, De Petrocellis L, Bellini G, Petrosino S et al (2009) The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption. Bone 44:476–484. doi: 10.1016/j.bone.2008.10.056 PubMedCrossRefGoogle Scholar
  118. Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO, Leonova J et al (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101. doi: 10.1038/sj.bjp.0707460 PubMedCrossRefGoogle Scholar
  119. Sawzdargo M, Nguyen T, Lee DK, Lynch KR, Cheng R, Heng HH et al (1999) Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain Res Mol Brain Res 64:193–198PubMedCrossRefGoogle Scholar
  120. Sharir H, Abood ME (2010) Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol Ther 126:301–313. doi: 10.1016/j.pharmthera.2010.02.004 PubMedCrossRefGoogle Scholar
  121. Shui C, Spelsberg TC, Riggs BL, Khosla S (2003) Changes in Runx2/Cbfa1 expression and activity during osteoblastic differentiation of human bone marrow stromal cells. J Bone Miner Res 18:213–221PubMedCrossRefGoogle Scholar
  122. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319PubMedCrossRefGoogle Scholar
  123. Sobacchi C, Frattini A, Guerrini MM, Abinun M, Pangrazio A, Susani L et al (2007) Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nat Genet 39:960–962. doi: 10.1038/ng2076 PubMedCrossRefGoogle Scholar
  124. Song I, Kim JH, Kim K, Jin HM, Youn BU, Kim N (2009) Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation. FEBS Lett 583:2435–2440. doi: 10.1016/j.febslet.2009.06.047 PubMedCrossRefGoogle Scholar
  125. Specker BL, Schoenau E (2005) Quantitative bone analysis in children: current methods and ­recommendations. J Pediatr 146:726–731. doi: 10.1016/j.jpeds.2005.02.002 PubMedCrossRefGoogle Scholar
  126. Spence A (1990) Basic human anatomy. Benjamin-Cummings Publishing Company, New YorkGoogle Scholar
  127. Stark Z, Savarirayan R (2009) Osteopetrosis. Orphanet J Rare Dis 4:5. doi: 10.1186/1750-1172-4-5 PubMedCrossRefGoogle Scholar
  128. Staton PC, Hatcher JP, Walker DJ, Morrison AD, Shapland EM, Hughes JP et al (2008) The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain 139:225–236. doi: 10.1016/j.pain.2008.04.006 PubMedCrossRefGoogle Scholar
  129. Sutphen R, Xu Y, Wilbanks GD, Fiorica J, Grendys EC Jr, LaPolla JP et al (2004) Lysophospholipids are potential biomarkers of ovarian cancer. Cancer Epidemiol Biomarkers Prev 13:1185–1191PubMedGoogle Scholar
  130. Syed F, Khosla S (2005) Mechanisms of sex steroid effects on bone. Biochem Biophys Res Commun 328:688–696. doi: 10.1016/j.bbrc.2004.11.097 PubMedCrossRefGoogle Scholar
  131. Takada Y, Irie N, Gresh L, Nakamura T, Kato S, Wagner EF et al (2009) Late expression of c-Fos during osteoclast differentiation determines osteoclast survival and bone mass. Bone 44:S137CrossRefGoogle Scholar
  132. Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K et al (2000) T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 408:600–605. doi: 10.1038/3504610210 PubMedCrossRefGoogle Scholar
  133. Takeda S (2008) Central control of bone remodelling. J Neuroendocrinol 20:802–807. doi: 10.1111/j.1365-2826.2008.01732.x PubMedCrossRefGoogle Scholar
  134. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL et al (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317PubMedCrossRefGoogle Scholar
  135. Tam J, Ofek O, Fride E, Ledent C, Gabet Y, Muller R et al (2006) Involvement of neuronal cannabinoid receptor CB1 in regulation of bone mass and bone remodeling. Mol Pharmacol 70:786–792. doi: 10.1124/mol.106.026435 PubMedCrossRefGoogle Scholar
  136. Tam J, Trembovler V, Di Marzo V, Petrosino S, Leo G, Alexandrovich A et al (2008) The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling. FASEB J 22:285–294. doi: 10.1096/fj.06-7957com PubMedCrossRefGoogle Scholar
  137. Van Poznak C, Nadal C (2006) Bone integrity and bone metastases in breast cancer. Curr Oncol Rep 8:22–28PubMedCrossRefGoogle Scholar
  138. Waguespack SG, Koller DL, White KE, Fishburn T, Carn G, Buckwalter KA et al (2003) Chloride channel 7 (ClCN7) gene mutations and autosomal dominant osteopetrosis, type II. J Bone Miner Res 18:1513–1518PubMedCrossRefGoogle Scholar
  139. Waldeck-Weiermair M, Zoratti C, Osibow K, Balenga N, Goessnitzer E, Waldhoer M et al (2008) Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression. J Cell Sci 121:1704–1717. doi: 10.1242/jcs.020958 PubMedCrossRefGoogle Scholar
  140. Wei B, Wang J, Bourne P, Yang Q, Hicks D, Bu H et al (2008) Bone metastasis is strongly associated with estrogen receptor-positive/progesterone receptor-negative breast carcinomas. Hum Pathol 39:1809–1815. doi: 10.1016/j.humpath.2008.05.010 PubMedCrossRefGoogle Scholar
  141. Weilbaecher KN, Motyckova G, Huber WE, Takemoto CM, Hemesath TJ, Xu Y et al (2001) Linkage of M-CSF signaling to Mitf, TFE3, and the osteoclast defect in Mitf(mi/mi) mice. Mol Cell 8:749–758PubMedCrossRefGoogle Scholar
  142. Wenger T, Ledent C, Csernus V, Gerendai I (2001) The central cannabinoid receptor inactivation suppresses endocrine reproductive functions. Biochem Biophys Res Commun 284:363–368PubMedCrossRefGoogle Scholar
  143. Whyte LS, Ryberg E, Sims NA, Ridge SA, Mackie K, Greasley PJ et al (2009) The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci 106(38):16511–16516. doi: 10.1073/pnas.0902743106 PubMedCrossRefGoogle Scholar
  144. Whyte LS, Ford L, Ridge SA, Cameron GA, Rogers MJ, Ross RA (2011) Cannabinoids and bone: endocannabinoids modulate human osteoclast function in vitro. Br J Pharmacol 165(8):2584–2597. doi: 10.1111/j.1476-5381.2011.01519.x;10.1111/j.1476-5381.2011.01519.x CrossRefGoogle Scholar
  145. Xiao YJ, Schwartz B, Washington M, Kennedy A, Webster K, Belinson J et al (2001) Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs nonmalignant ascitic fluids. Anal Biochem 290:302–313. doi: 10.1006/abio.2001.5000 PubMedCrossRefGoogle Scholar
  146. Yamaguchi A, Komori T, Suda T (2000) Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, Hedgehogs, and Cbfa1. Endocr Rev 21:393–411. doi: 10.1210/er.21.4.393 PubMedCrossRefGoogle Scholar
  147. Yang M, Kream BE (2008) Calcitonin induces expression of the inducible cAMP early repressor in osteoclasts. Endocrine 33:245–253. doi: 10.1007/s12020-008-9092-8 PubMedCrossRefGoogle Scholar
  148. Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H et al (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345:442–444. doi: 10.1038/345442a0 PubMedCrossRefGoogle Scholar
  149. Young MF (2003) Bone matrix proteins: their function, regulation, and relationship to osteoporosis. Osteoporos Int 14(suppl 3):S35–S42. doi: 10.1007/s00198-002-1342-7 PubMedGoogle Scholar
  150. Zhang D, Udagawa N, Nakamura I, Murakami H, Saito S, Yamasaki K et al (1995) The small GTP-binding protein, rho p21, is involved in bone resorption by regulating cytoskeletal organization in osteoclasts.  J Cell Sci 108:2285–2292 PubMedCrossRefGoogle Scholar
  151. Zhu LL, Zaidi S, Moonga BS, Troen BR, Sun L (2005) RANK-L induces the expression of NFATc1, but not of NFkappaB subunits during osteoclast formation. Biochem Biophys Res Commun 326:131–135. doi: 10.1016/j.bbrc.2004.10.212 PubMedCrossRefGoogle Scholar
  152. Zuardi AW (2008) Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr 30:271–280PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Institute of Medical SciencesUniversity of AberdeenAberdeenUK
  2. 2.Kosterlitz Centre for Therapeutics, Institute of Medical SciencesUniversity of AberdeenAberdeenUK

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