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Dissociation of Bone Resorption and Bone Formation in Adult Mice with a Non-Functional V-ATPase in Osteoclasts Leads to Increased Bone Strength

Henriksen, Kim; Flores Bjurström, Carmen LU ; Thomsen, Jesper S.; Bruel, Anne-Marie; Thudium, Christian S.; Neutzsky-Wulff, Anita V.; Langenbach, Geerling E. J.; Sims, Natalie; Askmyr, Maria LU and Martin, Thomas J., et al. (2011) In PLoS ONE 6(11).
Abstract
Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption. To shed light on the effect of uncoupling in adult mice with respect to bone strength, we transplanted irradiated three-month old normal mice with hematopoietic stem cells from control or oc/oc mice, which have defective acid secretion, and followed them for 12 to 28 weeks. Engraftment levels were assessed by flow cytometry of peripheral blood. Serum samples were collected every six weeks for measurement of bone turnover markers. At termination bones were... (More)
Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption. To shed light on the effect of uncoupling in adult mice with respect to bone strength, we transplanted irradiated three-month old normal mice with hematopoietic stem cells from control or oc/oc mice, which have defective acid secretion, and followed them for 12 to 28 weeks. Engraftment levels were assessed by flow cytometry of peripheral blood. Serum samples were collected every six weeks for measurement of bone turnover markers. At termination bones were collected for mu CT and mechanical testing. An engraftment level of 98% was obtained. From week 6 until termination bone resorption was significantly reduced, while the osteoclast number was increased when comparing oc/oc to controls. Bone formation was elevated at week 6, normalized at week 12, and reduced onwards. mu CT and mechanical analyses of femurs and vertebrae showed increased bone volume and bone strength of cortical and trabecular bone. In conclusion, these data show that attenuation of acid secretion in adult mice leads to uncoupling and improves bone strength. (Less)
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PLoS ONE
volume
6
issue
11
publisher
Public Library of Science
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  • wos:000297347700058
  • scopus:80455131301
ISSN
1932-6203
DOI
10.1371/journal.pone.0027482
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English
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yes
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5e155018-9ebc-442b-b018-f63b1bba65ca (old id 2378628)
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2012-04-02 09:19:35
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@article{5e155018-9ebc-442b-b018-f63b1bba65ca,
  abstract     = {Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption. To shed light on the effect of uncoupling in adult mice with respect to bone strength, we transplanted irradiated three-month old normal mice with hematopoietic stem cells from control or oc/oc mice, which have defective acid secretion, and followed them for 12 to 28 weeks. Engraftment levels were assessed by flow cytometry of peripheral blood. Serum samples were collected every six weeks for measurement of bone turnover markers. At termination bones were collected for mu CT and mechanical testing. An engraftment level of 98% was obtained. From week 6 until termination bone resorption was significantly reduced, while the osteoclast number was increased when comparing oc/oc to controls. Bone formation was elevated at week 6, normalized at week 12, and reduced onwards. mu CT and mechanical analyses of femurs and vertebrae showed increased bone volume and bone strength of cortical and trabecular bone. In conclusion, these data show that attenuation of acid secretion in adult mice leads to uncoupling and improves bone strength.},
  author       = {Henriksen, Kim and Flores Bjurström, Carmen and Thomsen, Jesper S. and Bruel, Anne-Marie and Thudium, Christian S. and Neutzsky-Wulff, Anita V. and Langenbach, Geerling E. J. and Sims, Natalie and Askmyr, Maria and Martin, Thomas J. and Everts, Vincent and Karsdal, Morten A. and Richter, Johan},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Dissociation of Bone Resorption and Bone Formation in Adult Mice with a Non-Functional V-ATPase in Osteoclasts Leads to Increased Bone Strength},
  url          = {http://dx.doi.org/10.1371/journal.pone.0027482},
  volume       = {6},
  year         = {2011},
}