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
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.
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Transplantation of nonfunctional osteoclasts in irradiated skeletally mature 3-month-old wild-type mice induced high trabecular bone volume, increased bone strength, and increased bone formation rate in trabecular bone.
“The finding that the transplantation of nonfunctional osteoclasts in irradiated skeletally mature 3-month-old wild-type mice induced a high trabecular bone volume, increased bone strength, and an increased bone formation rate in trabecular bone222 supports this concept.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [222]
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- Authors
- Thudium, C. S., Moscatelli, I., Flores, C., Thomsen, J. S., Brüel, A., Gudmann, N. S., Hauge, E.-M., Karsdal, M. A., Richter, J., & Henriksen, K.
- Affiliations
- Lund University (SE)
- Aarhus University (DK)
- Nordic Bioscience (Denmark) (DK)
- Aarhus University Hospital (DK)
- Corresponding author
- Thudium, Christian S.
- ORCID
- Venue
- Calcified Tissue International
- Published
- 2014-05-18
- Volume
- 95
- Issue
- 1
- Pages
- 83-93
- ISSN
- 0171-967X (ISSN-L)
- 1432-0827
- OpenAlex
- W2011503572
- Cited by
- 36
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 3
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Calcified Tissue International (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- 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, osteoclasts, bone remodeling, bone resorption, bone formation, osteoblasts, hematopoietic stem cell transplantation, RANK, TRACP-5b, bone strength, trabecular bone volume
- MeSH terms
- Animals, Biomechanical Phenomena, Bone Resorption, Disease Models, Animal, Female, Male, Mice, Mutant Strains, Osteoclasts, Osteogenesis, Osteopetrosis, Mice, X-Ray Microtomography
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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