Cited by 77Bone Metabolism and DiseasesBone health and osteoporosis researchOsteomyelitis and Bone Disorders Research

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

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Henriksen, Kim, Flores, Carmen, Thomsen, Jesper S., Brüel, Anne-Marie, Thudium, Christian S., Neutzsky-Wulff, Anita V., Langenbach, Geerling E. J., Sims, Natalie +5 more·2011·PLoS ONE

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 µCT 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. µCT 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.

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Crossref · 10.1371/journal.pone.0027482

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  • In models of osteoclast-rich osteopetrosis, bone formation is maintained or enhanced despite impairment of resorption activity, providing evidence that nonresorbing osteoclasts promote or maintain bone formation.

    “In fact, in models of osteoclast-rich OPT, bone formation is maintained or enhanced despite the impairment of resorption activity,224 thus providing evidence that nonresorbing osteoclasts promote/maintain bone formation.”

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  1. [51]Neutzsky-Wulff AV Karsdal MA Henriksen K 2008 Characterization of the bone phenotype in ClC-7-deficient mice. Calcif Tissue Int 83 425 437 18958510

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Authors
Henriksen, K., Flores, C., Thomsen, J. S., Brüel, A.-M., Thudium, C. S., Neutzsky-Wulff, A. V., Langenbach, G. E. J., Sims, N., Askmyr, M., Martin, T. J., Everts, V., Karsdal, M. A., & Richter, J.
Affiliations
  • Nordic Bioscience (Denmark) (DK)
  • Lund University (SE)
  • Aarhus University (DK)
  • Academic Center for Dentistry Amsterdam (NL)
Corresponding author
Henriksen, Kim
Venue
PLoS ONE
Published
2011-11-07
Volume
6
Issue
11
Pages
e27482
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2111252052
Cited by
77
References
69
Citations by year
2026: 2 · 2025: 1 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 8 · 2016: 9 · 2015: 8 · 2014: 6 · 2013: 14 · 2012: 7
FWCI
3.51
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • VU Research Portal (publishedVersion, other-oa)
  • UvA-DARE (University of Amsterdam) (submittedVersion, other-oa)
  • Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • Lund University Publications (Lund University) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • Stiftelsen för Strategisk Forskning
  • Lunds Universitet
  • NordForsk
  • Barncancerfonden
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
Keywords
osteopetrosis, bone resorption, bone formation, bone strength, hematopoietic stem cell transplantation, bone turnover markers, cortical and trabecular bone, bone volume
MeSH terms
Animals, Bone Resorption, Graft Survival, Osteoclasts, Osteogenesis, Osteopetrosis, Bone Density, Hematopoietic Stem Cell Transplantation, Vacuolar Proton-Translocating ATPases, Mice

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