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

Scientific paper - Original scientific paper

• Author: Petra Šimić
• Author: Jasminka Buljan Culej
• Author: Iva Orlić
• Author: Lovorka Grgurević
• Author: Nataša Drača
• Author: Radan Spaventi
• Author: Slobodan Vukičević
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences

Abstract (english)

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.

• Keywords (english): 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
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Journal of Biological Chemistry
• Numbering: vol. 281, no. 35, pp. 25509-25521
• p-ISSN: 0021-9258
• DOI: https://doi.org/10.1074/jbc.M513276200
• URN:NBN: urn:nbn:hr:105:368042
• Publication: 2006-09-01
• Document URL: http://www.jbc.org/content/281/35/25509.long
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 11:34:21