Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts
Abstract
The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts. Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic.
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Early reversal cells, located in close proximity to resorbing osteoclasts and forming direct cellular contacts with neighboring osteoclasts through short cytoplasmic extensions, are osteoblast progenitors with the capacity to digest fibrillar collagen remnants, similar to BLCs.
“Moreover, Abdelgawad et al.266 observed that early reversal cells, located in close proximity to resorbing osteoclasts and forming direct cellular contacts with neighboring osteoclasts through short cytoplasmic extensions, are osteoblast progenitors with the capacity to digest fibrillar collagen remnants, similar to BLCs.113”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [266]
Immunoreactivity of reversal cells for osteoclast-derived TRAcP is attributable to TRAcP taken up by osteoblast lines from neighboring osteoclasts and does not represent acquisition of an osteoclastic phenotype.
“Abdelgawad et al.266 showed that the immunoreactivity of these cells for osteoclast-derived TRAcP is attributable to TRAcP taken up by osteoblast lines from neighboring osteoclasts and does not represent the acquisition of an osteoclastic phenotype.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [266]
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- Authors
- Abdelgawad, M. E., Delaisse, J.-M., Hinge, M., Jensen, P. R., Alnaimi, R. W., Rolighed, L., Engelholm, L. H., Marcussen, N., & Andersen, T. L.
- Affiliations
- University of Southern Denmark (DK)
- Aarhus University Hospital (DK)
- University of Copenhagen (DK)
- Odense University Hospital (DK)
- Corresponding author
- Andersen, Thomas Levin
- ORCID
- Venue
- Histochemistry and Cell Biology
- Published
- 2016-02-09
- Volume
- 145
- Issue
- 6
- Pages
- 603-615
- ISSN
- 0948-6143 (ISSN-L)
- 1432-119X
- OpenAlex
- W2254323254
- Cited by
- 76
- References
- 58
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 7 · 2023: 9 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 4
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Histochemistry and Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Danish Soutern region research grant (09/13570)
- 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 › Bone and Dental Protein Studies
- Keywords
- bone remodeling, osteoclasts, osteoblasts, bone resorption, bone formation, Runx2, CD56, tartrate-resistant acid phosphatase, MMP-13, collagenase-3, collagen degradation, extracellular matrix, trabecular bone, osteoblast-osteoclast interaction
- MeSH terms
- Adult, Aged, Female, Humans, Male, Middle Aged, Osteoblasts, Osteoclasts, Bone Remodeling, Microscopy, Electron, Transmission, Hyperparathyroidism, Primary
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