Osteoclast synthesis and secretion and activation of latent transforming growth factor β

Oursler, Merry Jo

doi:10.1002/jbmr.5650090402

Cited by 157Bone Metabolism and DiseasesTGF-β signaling in diseasesProtease and Inhibitor Mechanisms

Osteoclast synthesis and secretion and activation of latent transforming growth factor β

Oursler, Merry Jo·1994·Journal of Bone and Mineral Research

DOI 10.1002/jbmr.5650090402

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Abstract

The coupling of bone resorption and formation suggests that autocrine and paracrine factors are produced and released within the local bone environment. Since osteoblasts secrete latent transforming growth factor β (TGF-β), and osteoclasts can activate this latent complex, one candidate paracrine coupling factor is TGF-β. To examine whether TGF-β is also a potential osteoclast-derived autocrine and paracrine factor, highly purified avian osteoclasts were examined for synthesis of TGF-β and the mechanism by which osteoclasts activate the latent TGF-β complex was investigated. TGF-β protein production was measured within 4 h of culture in osteoclast-conditioned media using growth factor inhibition of CCL-64 cells and verified by blocking effects with anti-TGF-β antibodies. Synthesis of TGF-β was confirmed by northern blotting and metabolic labeling. Northern blots of total RNA revealed that osteoclasts expressed the mRNA for TGF-β2, β3, and β4. Biosynthetic studies suggest that TGF-β2 was the principle form secreted in culture. Nearly all the TGF-β that was secreted had been activated by the osteoclasts. When presented with exogenous latent TGF-β, osteoclasts activated latent TGF-β from a variety of sources. Furthermore, osteoclast-conditioned media retained the ability to activate latent TGF-β during cell-free incubations at 37°C. Osteoclast-mediated activation was inhibited by proteinase inhibitors, weak base treatment of the cells, or disruption of the cytoskeletal network. These data suggest that osteoclasts may secrete proteinases into the extracellular milieu to activate latent TGF-β and that TGF-β may be an autocrine factor involved in regulating osteoclast activity.

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During bone resorption, osteoclasts lower pH in resorption lacunae and secrete cathepsin K, thus releasing and activating TGF-β1.
“This occurs during bone resorption since osteoclasts lower the pH in resorption lacunae and secrete cathepsin K, thus releasing and activating TGF-β1.202”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [202]

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Authors: Oursler, M. J.
Affiliations: Mayo Clinic (US)
Corresponding author: Oursler, Merry Jo
Venue: Journal of Bone and Mineral Research
Publisher: Oxford University Press (OUP)
Published: 1994-04-01
Volume: 9
Issue: 4
Pages: 443-452
ISSN: 0884-0431 (ISSN-L)
1523-4681
DOI: 10.1002/jbmr.5650090402
OpenAlex: W2043164695
Cited by: 153
References: 61
Citations by year: 2026: 1 · 2025: 1 · 2024: 5 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 6 · 2012: 5
FWCI: 2.02
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)
Funders: National Institutes of Health (AR4114-01A1)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords: osteoclasts, TGF-beta activation, TGF-beta secretion, autocrine regulation, paracrine signaling, bone resorption, bone formation, proteolytic enzymes, cytoskeleton, TGF-beta2, TGF-beta mRNA expression
MeSH terms: Animals, Bone Resorption, Cells, Cultured, Chickens, Osteoclasts, Osteogenesis, Protease Inhibitors, RNA, Messenger, Transforming Growth Factor beta

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Osteoclast synthesis and secretion and activation of latent transforming growth factor β

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