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A Comparison of Osteoclast-Rich and Osteoclast-Poor Osteopetrosis in Adult Mice Sheds Light on the Role of the Osteoclast in Coupling Bone Resorption and Bone Formation

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Author

  • Christian Thudium
  • Ilana Moscatelli
  • Carmen Flores Bjurström
  • Jesper S. Thomsen
  • Annemarie Bruel
  • Natasja Staehr Gudmann
  • Ellen-Margrethe Hauge
  • Morten A. Karsdal
  • Johan Richter
  • Kim Henriksen

Summary, in English

Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating that osteoclasts are important for regulating osteoblast activity. To illuminate the role of the osteoclast in controlling bone remodeling, we transplanted irradiated skeletally mature 3-month old wild-type mice with hematopoietic stem cells (HSCs) to generate either an osteoclast-rich or osteoclast-poor adult osteopetrosis model. We used fetal liver HSCs from (1) oc/oc mice, (2) RANK KO mice, and (3) compared these to wt control cells. TRAP5b activity, a marker of osteoclast number and size, was increased in the oc/oc recipients, while a significant reduction was seen in the RANK KO recipients. In contrast, the bone resorption marker CTX-I was similarly decreased in both groups. Both oc/oc and Rank KO recipients developed a mild osteopetrotic phenotype. However, the osteoclast-rich oc/oc recipients showed higher trabecular bone volume (40 %), increased bone strength (66 %), and increased bone formation rate (54 %) in trabecular bone, while RANK KO recipients showed only minor trends compared to control recipients. We here show that maintaining non-resorbing osteoclasts, as opposed to reducing the osteoclasts, leads to increased bone formation, bone volume, and ultimately higher bone strength in vivo, which indicates that osteoclasts are sources of anabolic molecules for the osteoblasts.

Publishing year

2014

Language

English

Pages

83-93

Publication/Series

Calcified Tissue International

Volume

95

Issue

1

Document type

Journal article

Publisher

Springer

Topic

  • Hematology

Keywords

  • Osteoclast
  • Osteopetrosis
  • Coupling
  • V-ATPase
  • Osteoblast
  • oc/oc mouse
  • RANK KO
  • HSC
  • MicroCT
  • Bone strength
  • Hematopoiesis

Status

Published

ISBN/ISSN/Other

  • ISSN: 1432-0827