Top

Published in:

01-12-2007 | Review

Interaction of bone morphogenetic proteins with cells of the osteoclast lineage: review of the existing evidence

Authors: P. V. Giannoudis, N. K. Kanakaris, T. A. Einhorn

Published in: Osteoporosis International | Issue 12/2007

Abstract

The present review evaluates the existing scientific proofs of this supplementary role of the BMPs and summarises its clinical implications. Bone regeneration is a process consisting of bone formation and bone resorption, two different but closely coupling pathways, which in most circumstances proceed simultaneously. Plenty of evidence has also characterised the bone morphogenetic proteins (BMPs) as inducing factors of bone formation. However, there is also evidence that these multifunctioning proteins affect bone resorption and the osteoclast homeostasis utilising various pathways. The present review evaluates the existing scientific evidence of this supplementary role of the BMPs, and summarises its clinical implications.

Olsen BR, Reginato AM, Wang W (2000) Bone development. Annu Rev Cell Dev Biol 16:191–220PubMedCrossRef

Einhorn TA, Lee CA (2001) Bone regeneration: new findings and potential clinical applications. J Am Acad Orthop Surg 9:157–165PubMed

Boskey AL, Posner AS (1984) Bone structure, composition, and mineralization. Orthop Clin North Am 15:597–612PubMed

Yoshikawa H, Takaoka K (1994) Bone remodelling and its regulators. Nippon Rinsho 52:2262–2267PubMed

Urist MR (1965) Bone: formation by autoinduction. Science 150:893–899PubMedCrossRef

Urist MR, Strates BS (1971) Bone morphogenetic protein. J Dent Res 50:1392–1406PubMed

Wozney JM, Rosen V, Celeste AJ et al (1988) Novel regulators of bone formation: molecular clones and activities. Science 242:1528–1534PubMedCrossRef

Wang EA, Rosen V, Cordes P et al (1988) Purification and characterization of other distinct bone-inducing factors. Proc Natl Acad Sci USA 85:9484–9488PubMedCrossRef

Wang EA, Rosen V, D’Alessandro JS et al (1990) Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA 87:2220–2224PubMedCrossRef

10.

Ozkaynak E, Rueger DC, Drier EA et al (1990) OP-1 cDNA encodes an osteogenic protein in the TGF-beta family. Embo J 9:2085–2093PubMed

11.

Bessho K, Kusumoto K, Fujimura K et al (1999) Comparison of recombinant and purified human bone morphogenetic protein. Br J Oral Maxillofac Surg 37:2–5PubMedCrossRef

12.

Sakou T (1998) Bone morphogenetic proteins: from basic studies to clinical approaches. Bone 22:591–603PubMedCrossRef

13.

Termaat MF, Den Boer FC, Bakker FC et al (2005) Bone morphogenetic proteins. Development and clinical efficacy in the treatment of fractures and bone defects. J Bone Joint Surg Am 87:1367–1378PubMedCrossRef

14.

Cheng H, Jiang W, Phillips FM et al (2003) Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 85-A:1544–1552PubMed

15.

Jung RE, Glauser R, Scharer P et al (2003) Effect of rhBMP-2 on guided bone regeneration in humans. Clin Oral Implants Res 14:556–568PubMedCrossRef

16.

Geesink RG, Hoefnagels NH, Bulstra SK (1999) Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect. J Bone Joint Surg Br 81:710–718PubMedCrossRef

17.

Tsumaki N, Yoshikawa H (2005) The role of bone morphogenetic proteins in endochondral bone formation. Cytokine Growth Factor Rev 16:279–285PubMedCrossRef

18.

Yamaguchi A, Katagiri T, Ikeda T et al (1991) Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro. J Cell Biol 113:681–687PubMedCrossRef

19.

Harwood PJ, Giannoudis PV (2005) Application of bone morphogenetic proteins in orthopaedic practice: their efficacy and side effects. Expert Opin Drug Saf 4:75–89PubMedCrossRef

20.

Dimitriou R, Dahabreh Z, Katsoulis E et al (2005) Application of recombinant BMP-7 on persistent upper and lower limb non-unions. Injury 36(Suppl 4):S51–S59PubMedCrossRef

21.

Wong RK, Hagg EU, Rabie AB et al (2002) Bone induction in clinical orthodontics: a review. Int J Adult Orthodon Orthognath Surg 17:140–149PubMed

22.

Trippel SB, Coutts RD, Einhorn TA et al (1996) Instructional course lectures, the American Academy of Orthopaedic Surgeons - growth factors as therapeutic agents. J Bone Joint Surg Am 78:1272–1286

23.

Cook SD (1999) Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites. Orthopedics 22:669–671PubMed

24.

Kain MS, Einhorn TA (2005) Recombinant human bone morphogenetic proteins in the treatment of fractures. Foot Ankle Clin 10:639–650, viiiPubMedCrossRef

25.

Meraw SJ, Reeve CM, Lohse CM et al (2000) Treatment of peri-implant defects with combination growth factor cement. J Periodontol 71:8–13PubMedCrossRef

26.

Cook SD, Barrack RL, Shimmin A et al (2001) The use of osteogenic protein-1 in reconstructive surgery of the hip. J Arthroplasty 16:88–94PubMedCrossRef

27.

Einhorn TA, Trippel SB (1997) Growth factor treatment of fractures. Instr Course Lect 46:483–486PubMed

28.

Friedlaender GE, Perry CR, Cole JD et al (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 83-A Suppl 1:S151–S158PubMed

29.

Einhorn TA (2003) Clinical applications of recombinant human BMPs: early experience and future development. J Bone Joint Surg Am 85-A Suppl 3:82–88PubMed

30.

Govender S, Csimma C, Genant HK et al (2002) Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am 84-A:2123–2134PubMed

31.

Sakata H, Takagi K (1987) Effect of bone marrow mononuclear phagocytes on the bone matrix-induced bone formation in rats. Clin Orthop Relat Res 253–258

32.

Tanaka S, Nakamura I, Inoue J et al (2003) Signal transduction pathways regulating osteoclast differentiation and function. J Bone Miner Metab 21:123–133PubMedCrossRef

33.

Serke S, Sauberlich S, Abe Y et al (1991) Analysis of CD34-positive hemopoietic progenitor cells from normal human adult peripheral blood: flow-cytometrical studies and in-vitro colony (CFU-GM, BFU-E) assays. Ann Hematol 62:45–53PubMedCrossRef

34.

Miyamoto T, Ohneda O, Arai F et al (2001) Bifurcation of osteoclasts and dendritic cells from common progenitors. Blood 98:2544–2554PubMedCrossRef

35.

Roodman GD (2006) Regulation of osteoclast differentiation. Ann N Y Acad Sci 1068:100–109PubMedCrossRef

36.

Dougall WC, Glaccum M, Charrier K et al (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424PubMedCrossRef

37.

Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMedCrossRef

38.

Otsuka E, Notoya M, Hagiwara H (2003) Treatment of myoblastic C2C12 cells with BMP-2 stimulates vitamin D-induced formation of osteoclasts. Calcif Tissue Int 73:72–77PubMedCrossRef

39.

Kanatani M, Sugimoto T, Kaji H et al (1995) Stimulatory effect of bone morphogenetic protein-2 on osteoclast-like cell formation and bone-resorbing activity. J Bone Miner Res 10:1681–1690PubMed

40.

Manolagas SC, Jilka RL (1995) Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 332:305–311PubMedCrossRef

41.

Choi SJ, Han JH, Roodman GD (2001) ADAM8: a novel osteoclast stimulating factor. J Bone Miner Res 16:814–822PubMedCrossRef

42.

Takahashi S, Reddy SV, Chirgwin JM et al (1994) Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption. J Biol Chem 269:28696–28701PubMed

43.

Udagawa N (2002) Mechanisms involved in bone resorption. Biogerontology 3:79–83PubMedCrossRef

44.

Suda T, Takahashi N, Udagawa N et al (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345–357PubMedCrossRef

45.

Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257PubMed

46.

Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306PubMed

47.

Koide M, Murase Y, Yamato K et al (1999) Bone morphogenetic protein-2 enhances osteoclast formation mediated by interleukin-1alpha through upregulation of osteoclast differentiation factor and cyclooxygenase-2. Biochem Biophys Res Commun 259:97–102PubMedCrossRef

48.

Suda T, Jimi E, Nakamura I et al (1997) Role of 1 alpha,25-dihydroxyvitamin D3 in osteoclast differentiation and function. Methods Enzymol 282:223–235PubMed

49.

Nicholson GC, Moseley JM, Sexton PM et al (1986) Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization. J Clin Invest 78:355–360PubMed

50.

Hattersley G, Chambers TJ (1989) Calcitonin receptors as markers for osteoclastic differentiation: correlation between generation of bone-resorptive cells and cells that express calcitonin receptors in mouse bone marrow cultures. Endocrinology 125:1606–1612PubMedCrossRef

51.

Takada Y, Kusuda M, Hiura K et al (1992) A simple method to assess osteoclast-mediated bone resorption using unfractionated bone cells. Bone Miner 17:347–359PubMedCrossRef

52.

Massague J (1996) TGFbeta signaling: receptors, transducers, and Mad proteins. Cell 85:947–950PubMedCrossRef

53.

Derynck R, Feng XH (1997) TGF-beta receptor signaling. Biochim Biophys Acta 1333:F105–F150PubMed

54.

Chen D, Zhao M, Mundy G (2004) Bone Morphogenetic Proteins. Growth Factors 22:233–241PubMedCrossRef

55.

Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 84-A:1032–1044PubMed

56.

Massague J, Wotton D (2000) Transcriptional control by the TGF-beta/Smad signaling system. Embo J 19:1745–1754PubMedCrossRef

57.

Granjeiro JM, Oliveira RC, Bustos-Valenzuela JC et al (2005) Bone morphogenetic proteins: from structure to clinical use. Braz J Med Biol Res 38:1463–1473PubMedCrossRef

58.

Canalis E, Economides AN, Gazzerro E (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 24:218–235PubMedCrossRef

59.

Kuriyama S, Lupo G, Ohta K et al (2006) Tsukushi controls ectodermal patterning and neural crest specification in Xenopus by direct regulation of BMP4 and X-delta-1 activity. Development 133:75–88PubMedCrossRef

60.

Yanagita M (2005) BMP antagonists: their roles in development and involvement in pathophysiology. Cytokine Growth Factor Rev 16:309–317PubMedCrossRef

61.

Cunningham NS, Paralkar V, Reddi AH (1992) Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor beta 1 mRNA expression. Proc Natl Acad Sci US`A 89:11740–11744PubMedCrossRef

62.

Hentunen TA, Cunningham NS, Vuolteenaho O et al (1994) Osteoclast recruiting activity in bone matrix. Bone Miner 25:183–198PubMedCrossRef

63.

Nakase T, Nomura S, Yoshikawa H et al (1994) Transient and localized expression of bone morphogenetic protein 4 messenger RNA during fracture healing. J Bone Miner Res 9:651–659PubMedCrossRef

64.

Hentunen TA, Lakkakorpi PT, Tuukkanen J et al (1995) Effects of recombinant human osteogenic protein-1 on the differentiation of osteoclast-like cells and bone resorption. Biochem Biophys Res Commun 209:433–443PubMedCrossRef

65.

Hodges PT, Baehner FL, Masuhara K et al (1997) Immunolocalization of bone morphogenetic protein-4 and -6 in human growth plate. Trans Orthop Res Soc 22:615

66.

Nishimura T, Simmons DJ, Mainous EG (1997) The origin of bone formed by heterotopic periosteal autografts. J Oral Maxillofac Surg 55:1265–1268PubMedCrossRef

67.

Helder MN, Karg H, Bervoets TJ et al (1998) Bone morphogenetic protein-7 (osteogenic protein-1, OP-1) and tooth development. J Dent Res 77:545–554PubMedCrossRef

68.

Hofbauer LC, Dunstan CR, Spelsberg TC et al (1998) Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines. Biochem Biophys Res Commun 250:776–781PubMedCrossRef

69.

Onishi T, Ishidou Y, Nagamine T et al (1998) Distinct and overlapping patterns of localization of bone morphogenetic protein (BMP) family members and a BMP type II receptor during fracture healing in rats. Bone 22:605–612PubMedCrossRef

70.

Anderson H, Hodges P, Moylan P (1999) Bone morphogenetic protein expression by cells of human and rat growth plate, metaphysis and articular cartilage. J Bone Miner Res 14(Suppl 1):S530–S539

71.

Abe E, Yamamoto M, Taguchi Y et al (2000) Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin. J Bone Miner Res 15:663–673PubMedCrossRef

72.

Anderson HC, Hodges PT, Aguilera XM et al (2000) Bone morphogenetic protein (BMP) localization in developing human and rat growth plate, metaphysis, epiphysis, and articular cartilage. J Histochem Cytochem 48:1493–1502PubMed

73.

Kaneko H, Arakawa T, Mano H et al (2000) Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts. Bone 27:479–486PubMedCrossRef

74.

Itoh K, Udagawa N, Katagiri T et al (2001) Bone morphogenetic protein 2 stimulates osteoclast differentiation and survival supported by receptor activator of nuclear factor-kappaB ligand. Endocrinology 142:3656–3662PubMedCrossRef

75.

Koseki T, Gao Y, Okahashi N et al (2002) Role of TGF-beta family in osteoclastogenesis induced by RANKL. Cell Signal 14:31–36PubMedCrossRef

76.

Irie K, Alpaslan C, Takahashi K et al (2003) Osteoclast differentiation in ectopic bone formation induced by recombinant human bone morphogenetic protein 2 (rhBMP-2). J Bone Miner Metab 21:363–369PubMedCrossRef

77.

Kusu N, Laurikkala J, Imanishi M et al (2003) Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity. J Biol Chem 278:24113–24117

78.

Mishina Y, Starbuck MW, Gentile MA et al (2004) Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling. J Biol Chem 279:27560–27566PubMedCrossRef

79.

Saito A, Suzuki Y, Ogata S et al (2004) Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide. J Biomed Mater Res A 70:115–121PubMedCrossRef

80.

Wise GE, Ding D, Yao S (2004) Regulation of secretion of osteoprotegerin in rat dental follicle cells. Eur J Oral Sci 112:439–444PubMedCrossRef

81.

Cowan CM, Aalami OO, Shi YY et al (2005) Bone morphogenetic protein 2 and retinoic acid accelerate in vivo bone formation, osteoclast recruitment, and bone turnover. Tissue Eng 11:645–658PubMedCrossRef

82.

Little DG, McDonald M, Bransford R et al (2005) Manipulation of the anabolic and catabolic responses with OP-1 and zoledronic acid in a rat critical defect model. J Bone Miner Res 20:2044–2052PubMedCrossRef

83.

Liu D, Yao S, Pan F et al (2005) Chronology and regulation of gene expression of RANKL in the rat dental follicle. Eur J Oral Sci 113:404–409PubMedCrossRef

84.

Takahashi D, Odajima T, Morita M et al (2005) Formation and resolution of ankylosis under application of recombinant human bone morphogenetic protein-2 (rhBMP-2) to class III furcation defects in cats. J Periodontal Res 40:299–305PubMedCrossRef

85.

Wildemann B, Kadow-Romacker A, Lubberstedt M et al (2005) Differences in the fusion and resorption activity of human osteoclasts after stimulation with different growth factors released from a polylactide carrier. Calcif Tissue Int 76:50–55PubMedCrossRef

86.

Feeley BT, Krenek L, Liu N et al (2006) Overexpression of noggin inhibits BMP-mediated growth of osteolytic prostate cancer lesions. Bone 38:154–166PubMedCrossRef

87.

Ghosh-Choudhury N, Singha PK, Woodruff K et al (2006) Concerted action of Smad and CREB-binding protein regulates bone morphogenetic protein-2-stimulated osteoblastic colony-stimulating factor-1 expression. J Biol Chem 281:20160–20170PubMedCrossRef

88.

Miyaji H, Sugaya T, Kato K et al (2006) Dentin resorption and cementum-like tissue formation by bone morphogenetic protein application. J Periodontal Res 41:311–315PubMedCrossRef

89.

Okamoto M, Murai J, Yoshikawa H et al (2006) Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. J Bone Miner Res 21:1022–1033PubMedCrossRef

90.

Wan C, He Q, Li G (2006) Osteoclastogenesis in the nonadherent cell population of human bone marrow is inhibited by rhBMP-2 alone or together with rhVEGF. J Orthop Res 24:29–36PubMedCrossRef

91.

Wutzl A, Brozek W, Lernbass I et al (2006) Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation. J Biomed Mater Res A 77:75–83PubMed

92.

Yamamoto Y, Udagawa N, Matsuura S et al (2006) Osteoblasts provide a suitable microenvironment for the action of receptor activator of nuclear factor-kappaB ligand. Endocrinology 147:3366–3374PubMedCrossRef

93.

Ellies DL, Viviano B, McCarthy J et al (2006) Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res 21:1738–1749PubMedCrossRef

94.

Poole KE, van Bezooijen RL, Loveridge N et al (2005) Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. Faseb J 19:1842–1844PubMed

95.

van Bezooijen RL, Roelen BA, Visser A et al (2004) Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med 199:805–814PubMedCrossRef

96.

Laursen M, Hoy K, Hansen ES et al (1999) Recombinant bone morphogenetic protein-7 as an intracorporal bone growth stimulator in unstable thoracolumbar burst fractures in humans: preliminary results. Eur Spine J 8:485–490PubMedCrossRef

97.

Pradhan BB, Bae HW, Dawson EG et al (2006) Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2. Spine 31:E277–E284PubMedCrossRef

98.

Jeppsson C, Astrand J, Tagil M et al (2003) A combination of bisphosphonate and BMP additives in impacted bone allografts. Acta Orthop Scand 74:483–489PubMedCrossRef

99.

Dimitriou R, Tsiridis E, Giannoudis PV (2005) Current concepts of molecular aspects of bone healing. Injury 36:1392–1404PubMedCrossRef

100.

Poynton AR, Lane JM (2002) Safety profile for the clinical use of bone morphogenetic proteins in the spine. Spine 27:S40–S48PubMedCrossRef

101.

Hansen SM, Sasso RC (2006) Resorptive response of rhBMP2 simulating infection in an anterior lumbar interbody fusion with a femoral ring. J Spinal Disord Tech 19:130–134PubMedCrossRef

102.

Höstner J, Karrhölm J, Hultmark P (2000) Early failures after femoral revisions using milled allograft bone mixed with OP-1. Poster Presentation. In SOF 2000. pp 205–206

Title: Interaction of bone morphogenetic proteins with cells of the osteoclast lineage: review of the existing evidence
Authors: P. V. Giannoudis
N. K. Kanakaris
T. A. Einhorn
Publication date: 01-12-2007
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 12/2007
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-007-0441-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Interaction of bone morphogenetic proteins with cells of the osteoclast lineage: review of the existing evidence

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 12/2007

Combining clinical factors and quantitative ultrasound improves the detection of women both at low and high risk for hip fracture

Family-based association study of ROR2 polymorphisms with an array of radiographic hand bone strength phenotypes

Mild prevalent and incident vertebral fractures are risk factors for new fractures

Effectiveness of antiresorptive agents in the prevention of recurrent hip fractures

An association between socioeconomic, health and health behavioural indicators and fractures in young adult males

Fractures during growth: potential role of a milk-free diet