The DOI matches its Crossref record; 57 of the 61 references it cites were found in a registry or an index.
Matrix metalloproteinases are obligatory for the migration of preosteoclasts to the developing marrow cavity of primitive long bones
Abstract
A key event in bone resorption is the recruitment of osteoclasts to future resorption sites. We follow here the migration of preosteoclasts from the periosteum to the developing marrow cavity of fetal mouse metatarsals in culture, and investigate the role of proteinases and demineralization in this migration. Our approach consisted in testing inhibitors of proteinases and demineralization on the migration kinetics. Migration was monitored by histomorphometry and the (pre)osteoclasts were identified by their tartrate resistant acid phosphatase (TRAP) activity. At the time of explantation, TRAP+ cells (all mononucleated) are detected only in the periosteum, and the core of the diaphysis (future marrow cavity) consists of calcified cartilage. Upon culture, TRAP+ cells (differentiating progressively into multinucleated osteoclasts) migrate through a seam of osteoid and a very thin and discontinuous layer of mineral, invade the calcified cartilage and transform it into a ‘marrow’ cavity; despite the passage of maturing osteoclasts, the osteoid develops into a bone collar. The migration of TRAP+ cells is completely prevented by matrix metalloproteinase (MMP) inhibitors, but not by a cysteine proteinase inhibitor, an inhibitor of carbonic anhydrase, or a bisphosphonate. The latter three drugs inhibit, however, the resorptive activity of mature osteoclasts at least as efficiently as do the MMP inhibitors, as assessed in cultures of calvariae and radii. Furthermore, in situ hybridizations reveal the expression of 2 MMPs, gelatinase B (MMP-9 or 92 kDa type IV collagenase) in (pre)osteoclasts, and interstitial collagenase (MMP-13) in hypertrophic chondrocytes. It is concluded that only MMPs appear obligatory for the migration of (pre)osteoclasts, and that this role is distinct from the one MMPs may play in the subosteoclastic resorption compartment. We propose that this new role of MMPs is a major component of the mechanism that determines where and when the osteoclasts will attack the bone.
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“MMP inhibitor administration fully prevented osteoclast recruitment in the diaphysis core in vivo145 as well as osteoclast migration through collagen in vitro.146”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [145]
Citations
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Proteases and Therapeutic Approaches of Bone Tumors
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Metadata
- Authors
- Blavier, L., & Delaissé, J. M.
- Affiliations
- UCLouvain (BE)
- ORCID
- Delaissé, J. M.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 1995-12-01
- Volume
- 108
- Issue
- 12
- Pages
- 3649-3659
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1953148896
- Cited by
- 221
- References
- 61
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 9 · 2018: 8 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 8 · 2012: 6
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
- Keywords
- matrix metalloproteinases, osteoclast recruitment, demineralization, MMP-9, MMP-13, bone resorption, osteoid, calcified cartilage, bisphosphonates, carbonic anhydrase inhibitors, cysteine protease inhibitors, hypertrophic chondrocytes, tartrate-resistant acid phosphatase
- MeSH terms
- Tartrate-Resistant Acid Phosphatase, Acid Phosphatase, Animals, Bone Marrow, Bone Marrow Cells, Bone Matrix, Bone Resorption, Cell Movement, Enzyme Inhibitors, Embryonic and Fetal Development, Isoenzymes, Kinetics, Metalloendopeptidases, Osteoclasts, Stem Cells, In Situ Hybridization, Mice
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