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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

Thudium, Christian LU ; Moscatelli, Ilana LU ; Flores Bjurström, Carmen LU ; Thomsen, Jesper S.; Bruel, Annemarie; Gudmann, Natasja Staehr; Hauge, Ellen-Margrethe; Karsdal, Morten A.; Richter, Johan LU and Henriksen, Kim (2014) In Calcified Tissue International 95(1). p.83-93
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Osteoclast, Osteopetrosis, Coupling, V-ATPase, Osteoblast, oc/oc mouse, RANK KO, HSC, MicroCT, Bone strength, Hematopoiesis
in
Calcified Tissue International
volume
95
issue
1
pages
83 - 93
publisher
Springer
external identifiers
  • wos:000337050000010
  • scopus:84902362257
ISSN
1432-0827
DOI
10.1007/s00223-014-9865-4
language
English
LU publication?
yes
id
122ca066-3ab0-4fe7-99bf-8df2fec66661 (old id 4549058)
date added to LUP
2014-08-01 07:37:28
date last changed
2017-10-22 04:16:19
@article{122ca066-3ab0-4fe7-99bf-8df2fec66661,
  abstract     = {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.},
  author       = {Thudium, Christian and Moscatelli, Ilana and Flores Bjurström, Carmen and Thomsen, Jesper S. and Bruel, Annemarie and Gudmann, Natasja Staehr and Hauge, Ellen-Margrethe and Karsdal, Morten A. and Richter, Johan and Henriksen, Kim},
  issn         = {1432-0827},
  keyword      = {Osteoclast,Osteopetrosis,Coupling,V-ATPase,Osteoblast,oc/oc mouse,RANK KO,HSC,MicroCT,Bone strength,Hematopoiesis},
  language     = {eng},
  number       = {1},
  pages        = {83--93},
  publisher    = {Springer},
  series       = {Calcified Tissue International},
  title        = {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},
  url          = {http://dx.doi.org/10.1007/s00223-014-9865-4},
  volume       = {95},
  year         = {2014},
}