Cited by 578Bone Metabolism and DiseasesCell death mechanisms and regulationBone health and osteoporosis research

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Osteoblast Programmed Cell Death (Apoptosis): Modulation by Growth Factors and Cytokines

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Jilka, Robert L., Weinstein, Robert S., Bellido, Teresita, Parfitt, A. Michael, Manolagas, Stavros C.·1998·Journal of Bone and Mineral Research

DOI 10.1359/jbmr.1998.13.5.793

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Abstract

Once osteoblasts have completed their bone-forming function, they are either entrapped in bone matrix and become osteocytes or remain on the surface as lining cells. Nonetheless, 50–70% of the osteoblasts initially present at the remodeling site cannot be accounted for after enumeration of lining cells and osteocytes. We hypothesized that the missing osteoblasts die by apoptosis and that growth factors and cytokines produced in the bone microenvironment influence this process. We report that murine osteoblastic MC3T3-E1 cells underwent apoptosis following removal of serum, or addition of tumor necrosis factor (TNF), as indicated by terminal deoxynucleotidyl transferase–mediated dUTP-nick end labeling and DNA fragmentation studies. Transforming growth factor-β and interleukin-6 (IL-6)–type cytokines had antiapoptotic effects because they were able to counteract the effect of serum starvation or TNF. In addition, anti-Fas antibody stimulated apoptosis of human osteoblastic MG-63 cells and IL-6–type cytokines prevented these changes. The induction of apoptosis in MG-63 cells was associated with an increase in the ratio of the proapoptotic protein bax to the antiapoptotic protein bcl-2, and oncostatin M prevented this change. Examination of undecalcified sections of murine cancellous bone revealed the presence of apoptotic cells, identified as osteoblasts by their proximity to osteoid seams and their juxtaposition to cuboidal osteoblasts. Assuming an osteoblast life span of 300 h and a prevalence of apoptosis of 0.6%, we calculated that the fraction that undergo this process in vivo can indeed account for the missing osteoblasts. These findings establish that osteoblasts undergo apoptosis and strongly suggest that the process can be modulated by growth factors and cytokines produced in the bone microenvironment.

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Authors: Jilka, R. L., Weinstein, R. S., Bellido, T., Parfitt, A. M., & Manolagas, S. C.
Affiliations: University of Arkansas Medical Center (US)
Corresponding author: Jilka, Robert L.
ORCID: Weinstein, Robert S.
Bellido, Teresita
Manolagas, Stavros C.
Venue: Journal of Bone and Mineral Research
Publisher: Oxford University Press (OUP)
Published: 1998-05-01
Volume: 13
Issue: 5
Pages: 793-802
ISSN: 0884-0431 (ISSN-L)
1523-4681
DOI: 10.1359/jbmr.1998.13.5.793
OpenAlex: W2075292460
Cited by: 578
References: 40
Citations by year: 2026: 6 · 2025: 4 · 2024: 19 · 2023: 14 · 2022: 10 · 2021: 17 · 2020: 12 · 2019: 16 · 2018: 21 · 2017: 17 · 2016: 17 · 2015: 17 · 2014: 20 · 2013: 21 · 2012: 24
FWCI: 10.20
Type: journal article
Language: en
Open access: bronze
doi.org
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 Institute on Aging (P01AG013918)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords: osteoblast apoptosis, programmed cell death, growth factors, cytokines, TGF-beta, interleukin-6, TNF-α, Fas, Bax/Bcl-2 ratio, oncostatin M, bone remodeling, osteocytes, bone lining cells, MC3T3-E1 cells, MG-63 cells, bone microenvironment
MeSH terms: Animals, Bone and Bones, Cell Line, Growth Substances, Humans, Osteoblasts, Recombinant Proteins, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Transforming Growth Factor beta, Bone Remodeling, Apoptosis, Receptors, Interleukin-6, Mice

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Osteoblast Programmed Cell Death (Apoptosis): Modulation by Growth Factors and Cytokines

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