The Bone Lining Cell: Its Role in Cleaning Howship's Lacunae and Initiating Bone Formation
Abstract
In this study we investigated the role of bone lining cells in the coordination of bone resorption and formation. Ultrastructural analysis of mouse long bones and calvariae revealed that bone lining cells enwrap and subsequently digest collagen fibrils protruding from Howship's lacunae that are left by osteoclasts. By using selective proteinase inhibitors we show that this digestion depends on matrix metalloproteinases and, to some extent, on serine proteinases. Autoradiography revealed that after the bone lining cells have finished cleaning, they deposit a thin layer of a collagenous matrix along the Howship's lacuna, in close association with an osteopontin-rich cement line. Collagenous matrix deposition was detected only in completely cleaned pits. In bone from pycnodysostotic patients and cathepsin K-deficient mice, conditions in which osteoclastic bone matrix digestion is greatly inhibited, bone matrix leftovers proved to be degraded by bone lining cells, thus indicating that the bone lining cell “rescues” bone remodeling in these anomalies. We conclude that removal of bone collagen left by osteoclasts in Howship's lacunae is an obligatory step in the link between bone resorption and formation, and that bone lining cells and matrix metalloproteinases are essential in this process.
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Bone lining cells seem to play an important role in coupling bone resorption to bone formation.
“The function of bone lining cells is not well clear, but these cells seem to play an important role in coupling bone resorption to bone formation [9].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [9]
While osteoclasts express both cathepsin K and MMPs, which contribute differently to bone resorption, BLCs do not express cathepsin K but can efficiently remove nonmineralized fibrillary collagen mediated through their highly active MMPs.
“While osteoclasts express both of these enzymes types, which contribute differently to bone resorption,120 BLCs do not express cathepsin K but can efficiently remove nonmineralized fibrillary collagen (present either on the quiescent bone surface or in resorption lacunae after osteoclastic activity)113 mediated through their highly active MMPs.121”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [113]
Similar to osteocytes, BLCs express intercellular adhesion molecule-1 (ICAM-1) to maintain functional contact with osteoblasts, osteoclast precursors and mature osteoclasts.
“Similar to osteocytes, BLCs express intercellular adhesion molecule-1 (ICAM-1) to maintain functional contact with osteoblasts, osteoclast precursors113 and mature osteoclasts.114”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [113]
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 [113]
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- Authors
- Everts, V., Delaissé, J. M., Korper, W., Jansen, D. C., Tigchelaar-Gutter, W., Saftig, P., & Beertsen, W.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Center for Clinical & Basic Research (DK)
- Academic Center for Dentistry Amsterdam (NL)
- Department of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- Department of Biochemistry, University of Goettingen, Goettingen, Germany
- Corresponding author
- Everts, V.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-01-01
- Volume
- 17
- Issue
- 1
- Pages
- 77-90
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2144207870
- Cited by
- 411
- References
- 57
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 14 · 2023: 26 · 2022: 21 · 2021: 32 · 2020: 27 · 2019: 14 · 2018: 17 · 2017: 13 · 2016: 8 · 2015: 23 · 2014: 11 · 2013: 32 · 2012: 20
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- GRO (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- VU Research Portal (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- bone lining cells, Howship's lacunae, bone resorption, bone formation, osteoclasts, matrix metalloproteinases, serine protease, collagen digestion, cement lines, osteopontin, bone remodeling, pycnodysostosis, cathepsin K, bone ultrastructure
- MeSH terms
- Animals, Bone and Bones, Bone Development, Bone Diseases, Metabolic, Bone Matrix, Bone Resorption, Cathepsins, Collagen, Cysteine Endopeptidases, Humans, Models, Biological, Osteoclasts, Bone Remodeling, Matrix Metalloproteinases, Culture Techniques, Mice, Cathepsin K
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