Repozitorij Medicinskog fakulteta Sveučilišta u Zagrebu

Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption

Šimić, Petra and Buljan Culej, Jasminka and Orlić, Iva and Grgurević, Lovorka and Drača, Nataša and Spaventi, Radan and Vukičević, Slobodan (2006) Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption. Journal of Biological Chemistry, 281 (35). pp. 25509-21. ISSN 0021-9258

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    Official URL: http://www.jbc.org/

    English abstract

    Although recombinant human bone morphogenetic proteins (BMPs) are used locally for treating bone defects in humans, their systemic effect on bone augmentation has not been explored. We have previously demonstrated that demineralized bone (DB) from ovariectomized (OVX) rats cannot induce bone formation when implanted ectopically at the subcutaneous site. Here we showed in vitro that 17beta-estradiol (E2) specifically induced expression of Bmp6 mRNA in MC3T3-E1 preosteoblastic cells and that bone extracts from OVX rats lack BMPs. Next we demonstrated that 125I-BMP-6 administered systemically accumulated in the skeleton and also restored the osteoinductive capacity of ectopically implanted DB from OVX rats. BMP-6 applied systemically to aged OVX rats significantly increased bone volume and mechanical characteristics of both the trabecular and cortical bone, the osteoblast surface, serum osteocalcin and osteoprotegerin levels, and decreased the osteoclast surface, serum C-telopeptide, and interleukin-6. E2 was significantly less effective, and was not synergistic with BMP-6. Animals that discontinued BMP-6 therapy maintained bone mineral density gains for another 12 weeks. BMP-6 increased in vivo the bone expression of Acvr-1, Bmpr1b, Smad5, alkaline phosphatase, and collagen type I and decreased expression of Bmp3 and BMP antagonists, chordin and cerberus. These results show, for the first time, that systemically administered BMP-6 restores the bone inductive capacity, microarchitecture, and quality of the skeleton in osteoporotic rats.

    Item Type: Article
    MeSH: Aging ; Animals ; Bone Density ; Bone Development ; Bone Morphogenetic Protein 6 ; Bone Morphogenetic Proteins/administration & dosage ; Bone Resorption ; Estradiol/metabolism ; Femur/pathology ; Mice ; Osteoblasts/metabolism ; Osteoporosis ; Rats ; Rats, Sprague-Dawley ; Tomography, X-Ray Computed
    Divisions: Katedra za anatomiju i kliničku anatomiju
    Depositing User: Marijan Šember
    Status: Published
    Creators:
    CreatorsEmail
    Šimić, Petra
    Buljan Culej, Jasminka
    Orlić, Iva
    Grgurević, Lovorka
    Drača, Nataša
    Spaventi, Radan
    Vukičević, Slobodan
    Date: 01 September 2006
    Date Deposited: 09 Mar 2010
    Last Modified: 23 Sep 2011 18:11
    Subjects: /
    Related URLs:
      URI: http://medlib.mef.hr/id/eprint/737

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