Original Article

You have full text access to this OnlineOpen article

Acute phosphate restriction leads to impaired fracture healing and resistance to BMP-2

  1. Nathan A Wigner1,
  2. Hilary F Luderer2,
  3. Megan K Cox2,†,
  4. Karen Sooy2,‡,
  5. Louis C Gerstenfeld1,
  6. Marie B Demay2,*

Article first published online: 14 DEC 2009

DOI: 10.1359/jbmr.091021

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 25, Issue 4, pages 724–733, April 2010

Additional Information

How to Cite

Wigner, N. A., Luderer, H. F., Cox, M. K., Sooy, K., Gerstenfeld, L. C. and Demay, M. B. (2010), Acute phosphate restriction leads to impaired fracture healing and resistance to BMP-2. J Bone Miner Res, 25: 724–733. doi: 10.1359/jbmr.091021

Author Information

  1. 1

    Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Boston University Medical Center, Boston, MA, USA

  2. 2

    Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA

  1. †

    Department of Cell Biology, University of Alabama at Birmingham, McCallum Basic Health Sciences Building, 1918 University Blvd., Birmingham, AL 35205, USA

  2. ‡

    Endocrinology Unit, Centre for Cardiovascular Sciences, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH164TJ Scotland, USA

*Endocrine Unit, Thier 11, Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114, USA.

Publication History

  1. Issue published online: 9 APR 2010
  2. Article first published online: 14 DEC 2009
  3. Accepted manuscript online: 27 JAN 2010 12:00AM EST
  4. Manuscript Accepted: 15 OCT 2009
  5. Manuscript Revised: 2 SEP 2009
  6. Manuscript Received: 28 MAY 2009

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (691K)

References

  • 1
    Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA. Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem. 2003; 88: 873–884.
    Direct Link:
  • 2
    Colnot C, Thompson Z, Miclau T, Werb Z, Helms JA. Altered fracture repair in the absence of MMP9. Development. 2003; 130: 4123–4133.
  • 3
    Gerstenfeld LC, Cho TJ, Kon T, et al. Impaired intramembranous bone formation during bone repair in the absence of tumor necrosis factor-alpha signaling. Cells Tissues Organs. 2001; 169: 285–294.
  • 4
    Shimoaka T, Kamekura S, Chikuda H, et al. Impairment of bone healing by insulin receptor substrate-1 deficiency. J Biol Chem. 2004; 279: 15314–15322.
  • 5
    Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O'Keefe RJ. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest. 2002; 109: 1405–1415.
  • 6
    Kayal RA, Tsatsas D, Bauer MA, et al. Diminished bone formation during diabetic fracture healing is related to the premature resorption of cartilage associated with increased osteoclast activity. J Bone Miner Res. 2007; 22: 560–568.
    Direct Link:
  • 7
    Gaston MS, Simpson AH. Inhibition of fracture healing. J Bone Joint Surg Br. 2007; 89: 1553–1560.
  • 8
    Arikawa T, Omura K, Morita I. Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells. J Cell Physiol. 2004; 200: 400–406.
    Direct Link:
  • 9
    Paralkar VM, Grasser WA, Mansolf AL, et al. Regulation of BMP-7 expression by retinoic acid and prostaglandin E2. J Cell Physiol. 2002; 190: 207–217.
    Direct Link:
  • 10
    Murnaghan M, Li G, Marsh DR. Nonsteroidal anti-inflammatory drug-induced fracture nonunion: an inhibition of angiogenesis? J Bone Joint Surg Am. 2006; 88: 140–147.
  • 11
    Earle KE, Seneviratne T, Shaker J, Shoback D. Fanconi's syndrome in HIV+ adults: report of three cases and literature review. J Bone Miner Res. 2004; 19: 714–721.
    Direct Link:
  • 12
    Linde R, Saxena A, Feldman D. Hypophosphatemic rickets presenting as recurring pedal stress fractures in a middle-aged woman. J Foot Ankle Surg. 2001; 40: 101–104.
  • 13
    Robinson RF, Casavant MJ, Nahata MC, Mahan JD. Metabolic bone disease after chronic antacid administration in an infant. Ann Pharmacother. 2004; 38: 265–268.
  • 14
    Sabbagh Y, Carpenter TO, Demay M. Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. Proc Natl Acad Sci USA. 2005; 102: 9637–9642.
  • 15
    Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med. 1992; 327: 1637–1642.
  • 16
    Jonsson KB, Zahradnik R, Larsson T, et al. Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med. 2003; 348: 1656–1663.
  • 17
    Bonnarens F, Einhorn TA. Production of a standard closed fracture in laboratory animal bone. J Orthop Res. 1984; 2: 97–101.
    Direct Link:
  • 18
    Donohue MM, Demay MB. Rickets in VDR null mice is secondary to decreased apoptosis of hypertrophic chondrocytes. Endocrinology. 2002; 143: 3691–3694.
  • 19
    Li YC, Pirro AE, Amling M, et al. Targeted ablation of the vitamin D receptor: an animal model of vitamin D–dependent rickets type II with alopecia. Proc Natl Acad Sci U S A. 1997; 94: 9831–9835.
  • 20
    Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997; 89: 747–754.
  • 21
    Nakashima K, Zhou X, Kunkel G, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002; 108: 17–29.
  • 22
    Saas J, Gebauer M, Jacobi C, Haag J, Takigawa M, Aigner T. The human chondrosarcoma HCS-2/8 cell line is responsive to BMP-7, but not to IL-1β. Front Biosci. 2005; 10: 2027–2035.
  • 23
    Bell NH. Vitamin D-dependent rickets type II. Calcif Tissue Int. 1980; 31: 89–91.
  • 24
    Bergwitz C, Roslin NM, Tieder M, et al. SLC34A3 Mutations in Patients with Hereditary Hypophosphatemic Rickets with Hypercalciuria Predict a Key Role for the Sodium-Phosphate Cotransporter NaPi-IIc in Maintaining Phosphate Homeostasis. Am J Hum Genet. 2006; 78: 179–192.
  • 25
    Kitanaka STK, Murayama A, Sato T, et al. Inactivating mutations in the 25-hydroxyvitamin D 1α-hydroxylase gene in patients with pseudovitamin D–deficiency rickets. N Engl J Med. 1998; 338: 653–661.
  • 26
    Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation: molecular clones and activities. Science. 1988; 242: 1528–1534.
  • 27
    Baltzer AW, Lattermann C, Whalen JD, et al. Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP2 gene. Gene Ther. 2000; 7: 734–739.
  • 28
    Ferraz FH, Schellini SA, Schellini RC, Pellizon CH, Hirai FE, Padovani CR. BMP implant associated with platelet-rich plasma in orbit fracture repair. Curr Eye Res. 2008; 33: 293–301.
  • 29
    Kanakaris NK, Calori GM, Verdonk R, et al. Application of BMP-7 to tibial non-unions: a 3-year multicenter experience. Injury. 2008; 39: S83–90.
  • 30
    Virk MS, Conduah A, Park SH, et al. Influence of short-term adenoviral vector and prolonged lentiviral vector mediated bone morphogenetic protein-2 expression on the quality of bone repair in a rat femoral defect model. Bone. 2008; 42: 921–931.
  • 31
    Dudley AT, Lyons KM, Robertson EJ. A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev. 1995; 9: 2795–2807.
  • 32
    Luo G, Hofmann C, Bronckers ALJJ, Sohocki M, Bradley A, Karsenty G. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev. 1995; 9: 2808–2820.
  • 33
    Bandyopadhyay A, Tsuji K, Cox K, Harfe BD, Rosen V, Tabin CJ. Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS Genet. 2006; 2: e216.
  • 34
    Capdevila J, Johnson RL. Endogenous and ectopic expression of noggin suggests a conserved mechanism for regulation of BMP function during limb and somite patterning. Dev Biol. 1998; 197: 205–217.
  • 35
    Pizette S, Niswander L. BMPs are required at two steps of limb chondrogenesis: formation of prechondrogenic condensations and their differentiation into chondrocytes. Dev Biol. 2000; 219: 237–249.
  • 36
    Chhabra A, Zijerdi D, Zhang J, Kline A, Balian G, Hurwitz S. BMP-14 deficiency inhibits long bone fracture healing: a biochemical, histologic, and radiographic assessment. J Orthop Trauma. 2005; 19: 629–634.
  • 37
    Tsuji K, Cox K, Bandyopadhyay A, Harfe BD, Tabin CJ, Rosen V. BMP4 is dispensable for skeletogenesis and fracture-healing in the limb. J Bone Joint Surg Am. 2008; 90: 14–18.
  • 38
    Tsuji K, Bandyopadhyay A, Harfe BD, et al. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet. 2006; 38: 1424–1429.
  • 39
    Bais MV, Wigner N, Young M, et al. BMP2 is essential for post natal osteogenesis but not for recruitment of osteogenic stem cells. Bone. 2009; 45: 254–266.
  • 40
    Sapkota G, Knockaert M, Alarcon C, Montalvo E, Brivanlou AH, Massague J. Dephosphorylation of the linker regions of Smad1 and Smad2/3 by small C-terminal domain phosphatases has distinct outcomes for bone morphogenetic protein and transforming growth factor-beta pathways. J Biol Chem. 2006; 281: 40412–40419.
  • 41
    Xu L, Yao X, Chen X, Lu P, Zhang B, Ip YT. Msk is required for nuclear import of TGF-β/BMP-activated Smads. J Cell Biol. 2007; 178: 981–994.
  • 42
    Andhare RA, Takahashi N, Knudson W, Knudson CB. Hyaluronan promotes the chondrocyte response to BMP-7. Osteoarthritis Cartilage. 2009; 17: 892–902.
  • 43
    Colnot C. Skeletal Cell Fate Decisions Within Periosteum and Bone Marrow During Bone Regeneration. J Bone Miner Res. 2009; 24: 274–282.
    Direct Link:
View Full Article (HTML) Get PDF (691K)