Osteoblast Programmed Cell Death (Apoptosis): Modulation by Growth Factors and Cytokines
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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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At the mature osteoblast stage, osteoblasts can undergo apoptosis or become osteocytes or bone lining cells.
“At this stage, the mature osteoblasts can undergo apoptosis or become osteocytes or bone lining cells [47, 48].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [48]
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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.
- 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
- 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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