Cited by 221Bone Metabolism and DiseasesProtease and Inhibitor MechanismsBone and Dental Protein Studies

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Matrix metalloproteinases are obligatory for the migration of preosteoclasts to the developing marrow cavity of primitive long bones

Blavier, L., Delaissé, J. M.·1995·Journal of Cell Science

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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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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
DOI: 10.1242/jcs.108.12.3649
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
Licence: www.biologists.com/user-licence-1-1/ (vor)
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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Matrix metalloproteinases are obligatory for the migration of preosteoclasts to the developing marrow cavity of primitive long bones

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