The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index.
Osteoblast Programmed Cell Death (Apoptosis): Modulation by Growth Factors and Cytokines
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S. A. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.493 · Cited by 9,444
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,344
Self-citationBone Histomorphometry : Standardization of Nomenclature, Symbols, and Units
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · Cited by 3,258
Self-citationSuppression of TNF-α-Induced Apoptosis by NF-κB
Antwerp, D. J. V., Martin, S. J., Kafri, T., Green, D. R., & Verma, I. M. (1996) · Science · doi:10.1126/science.274.5288.787 · Cited by 2,581
Mechanisms and Genes of Cellular Suicide
Steller, H. (1995) · Science · doi:10.1126/science.7878463 · Cited by 2,469
(2019) · Elsevier eBooks · doi:10.1016/c2015-1-01622-2 · Cited by 1,690
Manolagas, S. C., & Jilka, R. L. (1995) · New England Journal of Medicine · doi:10.1056/nejm199502023320506 · Cited by 1,670
Self-citationCompston, J. E. (1997) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1997.2431019.x · Cited by 1,383
Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo
Hughes, D. E., Wright, K. R., Uy, H. L., Sasaki, A., Yoneda, T., Roodman, D., Mundy, G. R., & Boyce, B. F. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650101008 · Cited by 1,039
Parfitt, A. M. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240550303 · Cited by 1,001
Self-citation
Research works printed but not linked: 3
- Arnott, 1995, Evidence for a role of programmed cell death in the regulation of bone formation in adult human bone, J Bone Miner Res, 10, S216
- Parfitt, 1990, Bone, Vol 1: The Osteoblast and Osteocyte, 351
- Bellido, 1997, gp130/STAT3 activation stimulates the transcription of the cyclin dependent kinase inhibitor p21WAF1,CIP1 gene in osteoblasts: A prerequisite for the biologic effects of IL-6 type cytokines, J Bone Miner Res, 12, S159
Cited by
Sorted by citations
Items 501–577 of 577
Study the Influence of Captopril on Bone Metabolism in Elderly Hypertensive Women
Mousa, Z. A., Al-Shawi, N. N., & Omar, A. A. (2018) · Iraqi Journal of Pharmaceutical Sciences · doi:10.31351/vol24iss1pp11-17 · Cited by 1
Molekulare Mechanismen altersspezifischer Veränderungen des Kalzium- und Knochenstoffwechsels
Jakob, F. J., & Schütze, N. (2004) · Springer eBooks · doi:10.1007/978-3-642-18741-4_13 · Cited by 1
Stem cells in bone formation growth and remodeling
Jilka, R. L., & PARFITT, A. M. (2002) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(02)09049-1 · Cited by 1
Self-citationCoetzee, M. (2006) · UpSpace Institutional Repository (University of Pretoria) · Cited by 1
Hernández, M. V. (2006) · Revista Española de Enfermedades Metabólicas Óseas · doi:10.1016/s1132-8460(06)75263-1 · Cited by 1
Glucocorticoid osteoporosis - relations to BMU theory and to bone cell birth and death
PARFITT, A. M. (2001) · BoneKEy-Osteovision · doi:10.1138/2001026 · Cited by 1
Self-citationSequential gene expression determines optimal bone cell function
Gordeladze (2000) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2000.00644.x · Cited by 1
Proliferations- und Differenzierungsverhalten humaner Zahnkeimzellen der Pulpa
Gümmer, A. M. (2011) · doi:10.53846/goediss-1114 · Cited by 1
Porter, R. M. (2002) · VTechWorks (Virginia Tech) · Cited by 1
Graef, J. L. (2016) · SHAREOK (University of Oklahoma; Oklahoma State University; Central Oklahoma University) · Cited by 1
Synthesis of hydroxyapatite nanoparticles for polynucleotides delivery in dentistry
Thepphanao, N. (2018) · doi:10.58837/chula.the.2018.106 · Cited by 1
“6; they can be embedded in bone matrix as osteocytes, formed clusters cover the bone surface as lining cells, or undergo apoptosis.[32] Indeed, the osteocyte is also considered as an important cell that involve in the bone remodeling cycle by act as a mechanosensor that provides the signal for regulating the action of…”
BackgroundReduced order modelling of bone resorption and formation.
Moroz, A. (2011) · DMU Open Research Archive (De Montfort University) · Cited by 1
An Agent-based Model for Evaluating Cellular Mechanisms of Bone Remodeling
Schutte, L. (2012) · KiltHub Repository · doi:10.1184/r1/6714668
Estudis d'associació i funcionals en gens candidats per a l'osteoporosi
Pineda, M. B. (2007) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Osteogenetic growth factors around loosened hip replacements
Waris, V. J. (2014) · Työväentutkimus Vuosikirja
Factors affecting growth, differentiation and apoptosis of osteoblastic and osteosarcoma cells
Li, Y. (2008) · Figshare
Supanchart, C. (2009) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-7105
Adams, C. S., & Horton, W. E. (2001) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(01)06010-2
Mineral ions and osteoblast apoptosis
Nissenson, R. A. (2001) · BoneKEy-Osteovision · doi:10.1138/2001039
OSTEOPOROSIS AND METABOLIC BONE DISEASE IN LUPUS
Gluck, O. S., & Maricic, M. J. (2004) · Elsevier eBooks · doi:10.1016/b9-78-012433-9/01950-0417
The role of B cells in bone turnover in rheumatoid arthritis
Elshahaly, M. H., Wheater, G., Tuck, S. P., Datta, H. K., & van Laar, J. M. (2012) · International Journal of Clinical Rheumatology · doi:10.2217/ijr.12.5
Osteoimmunology: Interplay Between the Immune System and Bone
Walsh, M. C., Kim, N., Kadono, Y., Rho, J., Lee, S. Y., Lorenzo, J., & Choi, Y. (2006)
Lin, C.-D., Jeng, F.-C., Cheng, Y.-K., Lin, T., Chow, K., & Tsai, M.-H. (2004) · Zhōngtáiwān yīxué kēxué zázhì · doi:10.6558/mtjm.2004.9(4).1
Modelação matemática para avaliar o risco de fratura por desmineralização óssea
Teixeira, D. J. S. (2014) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Bone Response to Cyclooxygenase Inhibition and Mechanical Loading
Hackfort, B. T. (2014) · Creighton Digital Repository (CDR)
HIV infection, bone metabolism, and fractures Infecção pelo HIV, o metabolismo ósseo e fraturas
Prieto‐Alhambra, D., Musculoskeletal, O. N., Lifecourse, M., & Gol-Primary, I. J. (2014)
BISPHOSPHONATE-ASSOCIATEDOSTEOMYELITISOFTHEJAW: GUIDELINESFORPRACTICINGCLINICIANS
Wimalawansa, S. J. (2008)
Omar, S. M. M., Sweed, H. S., Abulsaad, K. A., & Sharara, S. M. (2014) · The Egyptian Journal of Histology · doi:10.1097/01.ehx.0000455271.60795.a7
The Role of the Interleukin-6 Family of Cytokines in Bone Remodeling and Bone Cancer
Blanchard, F., David, E., & Royer, B. B.-L. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374895-9.00008-6
Histomorphology of Osteoporotic Bone
Schnitzler, C. M. (2002) · CRC Press eBooks · doi:10.1201/b14228-4
Mechanically-Induced Osteocyte-Th17-Cell Signaling and Osteoclastogenesis
McCumber, T. L. (2016) · Creighton Digital Repository (CDR)
Das Organ Knochen – Histologie und Zellmechanismen
Seubert, B., van Griensven, M., & Balmayor, E. R. (2016) · Springer eBooks · doi:10.1007/978-3-642-44991-8_1
Drug-induced bone regeneration in a diabetic model
da Silva, J. C. O. R. (2017) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/2kh7-wb32
Efeito do cálcio extracelular na osteogénese através da regulação do calcium sensing receptor
Rego, L. C. F. F. D. N. (2005) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/tk3k-mn57
Targeting bone-microenvironment-tumour cell interactions : IGF-1 receptor kinase inhibitors
Logan, J. G. (2012) · ERA
Pathogenesis of Inflammation-Induced Bone Loss
Humphrey, M. B., & Nakamura, M. C. (2006) · Elsevier eBooks · doi:10.1016/b978-0-323-03437-1.50032-4
Almela, T. (2018) · White Rose eTheses Online (University of Leeds, The University of Sheffield, University of York)
Barbosa, A. P. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2019.tde-21082019-092319
Abnormal bone turnover in long-standing Crohn's disease in remission
Choon, E. J. S., Eerling, B. G. G., Churgers, L. J. S., Rummer, R., & Tockbrugger, R. W. S. (2001)
Kallio, A. (2008) · UTUPub (University of Turku)
Osteocytes and bone tumor niche
Terpos, E., & Christoulas, D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821666-8.00057-8
Novel cytokines in growth control and bone disease of multiple myeloma
Hjorth‐Hansen, H. (2001) · BIBSYS Brage (BIBSYS (Norway))
Involvement of osteocytes in cancer bone niche
Terpos, E., & Christoulas, D. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-416721-6.00006-6
Suva, L. J. (2010) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.2645956.2309054
Gimble, J. M., Floyd, Z. E., Kassem, M. S., & NUTTALL, M. E. (2009) · Springer eBooks · doi:10.1007/978-1-84628-697-1_2
“Pioneering studies by Jilka and colleagues demonstrated that cytokines such as TNF induced apoptosis in MSC-like cell lines in vitro (113).”
BackgroundKerschan‐Schindl, K., Nebot, E., & Pietschmann, P. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_153
Tantawy, A. H., ATTIA, H. F., Elzoghby, E. M., & Emam, M. A. (2022) · Benha Veterinary Medical Journal · doi:10.21608/bvmj.2021.92683.1466
“The bone formation rate was depended on number and activity of osteoblasts and osteocytes (Parfitt, 1990; Jilka et al., 1998).”
BackgroundRubin, F., Lacan, A., Halimi, P., & Bonfils, P. (2017) · EMC - Otorrinolaringología · doi:10.1016/s1632-3475(17)83972-2
Burr, D. B., Bellido, T., & White, K. E. (2011) · Elsevier eBooks · doi:10.1016/b978-0-323-06551-1.00009-9
Self-citationProietto, J. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736478587.793577682
Zuluaga, L. P. R., Restrepo, M. I. R., Bermúdez, J. D. O., & Díaz-Vallejo, J. A. (2021) · Revista Médicas UIS · doi:10.18273/revmed.v34n1-2021013
Mohan, S. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736222451.793564125
Omosule, C. L. (2021) · MOspace Institutional Repository (University of Missouri) · doi:10.32469/10355/90078
Alrabeah, G. O., Knowles, J. C., & Petridis, H. P. (2023) · Applied Sciences · doi:10.3390/app13158957
“The observed cytotoxic responses in osteoblastic cells could be due to metal ion release from the immersed samples into the surrounding medium as a result of corrosion, suggesting that corrosion products could play a pivotal role in the mediation of crestal bone loss around dental implants.”
BackgroundFarr, J. N., & Chandra, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15500-0.00017-7
Cheng, W., Liu, W. Y., & Gui, L. (2024) · Journal of Craniofacial Surgery · doi:10.1097/scs.0000000000010836
Effects of interleukin-4 and interleukin-13 on bone.
Silfverswärd, C. (2008) · Uppsala University Publications (Uppsala University)
Melemedjian, O. K. (2007) · UA Campus Repository (The University of Arizona)
Two-dimentional complex modeling of bone and joint infections using agent-based simulation
Alsassa, S. (2019) · theses.fr (ABES) · doi:10.70675/5dde1efcza50dz454azb715z5fccb48fd646
“, 2000) Osteoblasts production-rate 4 cell/day (Franchimont et al., 2000; Jilka et al., 2007; Ryser et al., 2009) Osteoblasts lifespan 3 months (Kollet et al.”
Sergheraert, J. (2023) · theses.fr (ABES) · doi:10.70675/18e53311z2e21z4c03zb0c3z5d816afda432
Marro, F. C. (2023) · theses.fr (ABES) · doi:10.70675/603309adz9f05z41efzba56zb4bb56eb7679
Demir, A. A., Combriat, T. M. D., Heyward, C. A., Tiainen, H., Carlier, A., & Dysthe, D. K. (2026) · Frontiers in Systems Biology · doi:10.3389/fsysb.2026.1872774
“The compound modulation functions are defined below.”
Autophagy in Osx1-Cre-targeted cells is essential for development, growth, and maintenance of bone
James, A., Kadhim, I., Laster, J., Khanal, V., Thostenson, J. D., Dole, N. S., Xiong, J., Nookaew, I., & Onal, M. (2026) · Bone Reports · doi:10.1016/j.bonr.2026.101941
“…of either pathway can inhibit maturation of osteoblasts and induce apoptosis (Abbas et al., 2003; Alliston et al., 2001; Gilbert et al., 2000; Jilka et al., 1998; Liu, 2025; Maeda et al., 2004), which is consistent with reduced osteoblast numbers in Osx1-Cre;Atg7 fl/fl mice (Li et al., 2018;…”
Chen, Y.-S., Ou, M.-S., & Lin, H. (2026) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.6c01225
Altaleb, J., Hansen, U., Abel, R. L., & Mudway, I. (2026) · The Innovation Life · doi:10.59717/j.xinn-life.2026.100247
Wu, Z., & Shao, G. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1945454
“…and deterioration of bone microarchitecture are common outcomes, upstream causes differ among postmenopausal, diabetic, glucocorticoid-induced, ageing-related, and iron-overload-related osteoporosis, as well as in fl ammatory bone loss (8, 13, 14, 17, 19 – 21, 25, 27 – 32, 66 – 68, 79, 124 – 129).”
Manolagas, S. C. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-018-6_18
Self-citation
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
