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

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 access

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

Open this paper in CoChat — free account Open PDF

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.

Integrity signals

Registry

Crossref · 10.1359/jbmr.1998.13.5.793

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

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
Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee
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-citation
Bone 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-citation
Suppression 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
Principles of Bone Biology
(2019) · Elsevier eBooks · doi:10.1016/c2015-1-01622-2 · Cited by 1,690
Bone Marrow, Cytokines, and Bone Remodeling — Emerging Insights into the Pathophysiology of Osteoporosis
Manolagas, S. C., & Jilka, R. L. (1995) · New England Journal of Medicine · doi:10.1056/nejm199502023320506 · Cited by 1,670
Self-citation
Principles of Bone Biology
Compston, 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
Osteonal and hemi‐osteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone
Parfitt, A. M. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240550303 · Cited by 1,001
Self-citation

Show all 40 references

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

Sorted by citations

Items 301–400 of 577

The Role of the Interleukin‐6/gp130 Signaling Pathway in Bone Metabolism
Liu, X., Kirschenbaum, A. M., Yao, S., & Levine, A. C. (2006) · Vitamins and hormones · doi:10.1016/s0083-6729(06)74014-6 · Cited by 30
Posttransplant bone disease
Rix, M., Lewin, E., & Ølgaard, K. (2003) · Transplantation Reviews · doi:10.1016/j.trre.2003.08.003 · Cited by 30
Loss of B cell regulatory function is associated with delayed healing in patients with tibia fracture
Yang, S., Ding, W., Feng, D., Gong, H., Zhu, D., Chen, B., & Chen, J. (2015) · APMIS · doi:10.1111/apm.12439 · Cited by 29
“TNF-a was also found to inhibit osteoblast differentiation and promote osteoblast apoptosis (9, 10).”
Background
Enterococcus faecalis induces apoptosis and pyroptosis of human osteoblastic MG 63 cells via the NLRP 3 inflammasome
Ran, S., Chu, M., Gu, S., Wang, J., & Liang, J. (2018) · International Endodontic Journal · doi:10.1111/iej.12965 · Cited by 29
BMP9 is a potential therapeutic agent for use in oral and maxillofacial bone tissue engineering
Liu, L., Chen, Y., Song, D., & Huang, D. (2020) · Biochemical Society Transactions · doi:10.1042/bst20200376 · Cited by 28
Cannabinoid Receptors as Target for Treatment of Osteoporosis: A Tale of Two Therapies
Idris, A. I. (2010) · Current Neuropharmacology · doi:10.2174/157015910792246173 · Cited by 29
“The average lifespan of human osteoblasts is three month, after which approximately 65% of functioning osteoblasts undergo apoptosis [49].”
Background
Apoptosis of Bone Cells
Jilka, R. L., Bellido, T., Almeida, M., Plotkin, L. I., O’Brien, C. A., Weinstein, R. S., & Manolagas, S. C. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00032-x · Cited by 30
Self-citation
Effects of 1α,25-Dihydroxyvitamin D3 and Growth Hormone on Apoptosis and Proliferation in UMR 106 Osteoblast-Like Cells
Morales, O., Samuelsson, M. K. R., Lindgren, U., & Haldosén, L.-A. (2003) · Endocrinology · doi:10.1210/en.2003-0718 · Cited by 29
Modulation of osteoblast gap junction connectivity by serum, TNFα, and TRAIL
Sharrow, A. C., Li, Y., Micsenyi, A., Griswold, R. D., Wells, A. H., Monga, S. P., & Blair, H. C. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.10.010 · Cited by 29
“TNFα or TRAIL do not cause osteoblast apoptosis acutely under most conditions, although some osteoblast-like cells can be sensitized for TNF apoptosis by inhibitors of protein synthesis or by special growth conditions [9,16-19].”
Background
Osteocytes regulate osteoblast differentiation and osteoclast activity through Interleukin-6 under mechanical loading
Hao, Z., Ma, Y., Wu, J., Li, X., Chen, H., Shen, J., & Wang, H. (2017) · RSC Advances · doi:10.1039/c7ra09308j · Cited by 28
Effects of bioactive peptides isoleucine-proline-proline (IPP), valine-proline-proline (VPP) and leucine-lysine-proline (LKP) on gene expression of osteoblasts differentiated from human mesenchymal stem cells.
Huttunen, M. M., Pekkinen, M., Ahlström, M., & Lamberg-Allardt, C. (2007) · British Journal of Nutrition · doi:10.1017/s0007114507744434 · Cited by 26
“Jilka et al.(41) have shown osteoblast apoptosis to be under the regulatory control of factors produced in the bone microenvironment.”
Background
The small GTPase RhoA is crucial for MC3T3‐E1 osteoblastic cell survival
Yoshida, T., Clark, M. F., & Stern, P. H. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22059 · Cited by 28
Effect of immobilized cell‐binding peptides on chitosan membranes for osteoblastic differentiation of mesenchymal stem cells
Lee, J., Choo, J., Choi, Y., Shim, I. K., Lee, S., Seol, Y., Chung, C., & Park, Y. (2008) · Biotechnology and Applied Biochemistry · doi:10.1042/ba20070169 · Cited by 28
The effects of dexamethasone on the apoptosis and osteogenic differentiation of human periodontal ligament cells
Kim, S., Kim, Y., Park, J., Lee, J., & Suh, J. (2013) · Journal of Periodontal & Implant Science · doi:10.5051/jpis.2013.43.4.168 · Cited by 28
“The “missing” osteoblasts appear to have died, possibly by apoptosis, and if apoptosis does occur in osteoblasts or their progenitors, osteoblastogenesis might be diminished [16].”
Background
New Concepts in Bone Remodeling
Dempster, D., & Zhou, H. (2006) · Elsevier eBooks · doi:10.1016/b9-78-012088-5/62650-0236 · Cited by 28
Cytokine-induced nitric-oxide-dependent apoptosis in mouse osteoblastic cells: Involvement of p38MAP kinase
Kuzushima, M., Mogi, M., & Togari, A. (2006) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2006.05.004 · Cited by 27
Ceramide-induced cell death/survival in murine osteoblasts
Hill, P., & Tumber, A. (2010) · Journal of Endocrinology · doi:10.1677/joe-10-0068 · Cited by 27
“Up to 65% of osteoblasts that originate at the remodelling site die by apoptosis, or programmed cell death (PCD), a process common to several regenerating tissues ( Jilka et al. 1998).”
Background
Alveolar Bone Regeneration by Implantation of Nacre and B-Tricalcium Phosphate in Guinea Pig
Asvanund, P., & CHUNHABUNDIT, P. (2012) · Implant Dentistry · doi:10.1097/id.0b013e3182563ae0 · Cited by 27
Large-scale gene expression analysis of osteoblasts cultured on three different Ti–6Al–4V surface treatments
Ku, C.-H., Browne, M., Gregson, P. J., Corbeil, J., & Pioletti, D. P. (2002) · Biomaterials · doi:10.1016/s0142-9612(02)00161-8 · Cited by 27
“Without the expression of NF-kB, or CSFs, osteoblasts are unable to secrete cytokines such as IL-1 or IL6 involved in the differentiation and apoptosis of osteoclasts [25, 26, 29].”
Background
Assembling the Puzzle Pieces. Insights for in Vitro Bone Remodeling
Krasnova, O. A., & Neganova, I. E. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10558-6 · Cited by 26
“The three possible fates for osteoblasts upon the completion of their primary boneforming function are: (1) becoming quiescent flat bone lining cells (BLCs), that participate in bone remodeling and form a barrier between the bone surface and the surrounding microenvironment [101]; (2) dying by apoptosis [102]; (3) and…”
Background
Matrix regulation of skeletal cell apoptosis III: Mechanism of ion pair‐induced apoptosis
Saunders, R., Szymczyk, K. H., Shapiro, I. M., & Adams, C. S. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21001 · Cited by 26
“This observation may help to explain why osteoblast apoptosis is most marked at sites of rapid bone formation or resorption [Bronckers et al., 1996; Noble et al., 1997; Jilka et al., 1998, 1999; Weinstein et al., 1998].”
Background
Competitive colonization of prosthetic surfaces bystaphylococcus aureusand human cells
Pérez‐Tanoira, R., Han, X., Soininen, A., Aarnisalo, A. A., Tiainen, V., Eklund, K. K., Esteban, J., & Kinnari, T. J. (2016) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.35863 · Cited by 25
“aureus-induced apoptosis of osteoblasts involves activation of caspase-8, which is an initiator caspase activated in death receptor-mediated apoptosis pathways.(38,39) The materials that promoted SaOS-2 cell adhesion enhanced also bacterial adherence and formation of biofilm biomass, however a higher hOB cell adherenc…”
Background
Effect of Ca-P compound formed by hydrothermal treatment on biodegradation and biocompatibility of Mg-3Al-1Zn-1.5Ca alloy; in vitro and in vivo evaluation
Kim, Y., Jang, Y., Lee, Y., Yi, H., Bae, T., & Lee, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-00656-0 · Cited by 25
Caspase-9 driven murine model of selective cell apoptosis and efferocytosis
Batoon, L., Koh, A. J., Kannan, R., McCauley, L. K., & Roca, H. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05594-6 · Cited by 25
“When considering the three fates of osteoblasts (osteocytes, bonelining cells, apoptosis), the greatest numbers undergo cell death (40–70%) [41].”
Background
Bone-Targeted Overexpression of Bcl-2 Increases Osteoblast Adhesion and Differentiation and Inhibits Mineralization In Vitro
Zhang, W., Pantschenko, A. G., McCarthy, M.-B., & Gronowicz, G. (2007) · Calcified Tissue International · doi:10.1007/s00223-006-0168-2 · Cited by 25
“Bcl-2 mice exhibit disorganized collagen deposition and mild growth plate abnormality at 35 days of age [11], indicating that Bcl-2 may be important in regulating bone growth and development, a process involving extensive chondrocyte and osteoblast apoptosis [12, 13].”
Background
The Molecular Genetics of Bone Formation
Marie, P. J. (2001) · American Journal of PharmacoGenomics · doi:10.2165/00129785-200101030-00003 · Cited by 25
Parathyroid hormone signaling in mature osteoblasts/osteocytes protects mice from age-related bone loss
Uda, Y., Saini, V., Petty, C. A., Alshehri, M., Shi, C., Spatz, J. M., Santos, R., Newell, C. M., Huang, T. Y., Kochen, A., et al. (2021) · Aging · doi:10.18632/aging.203808 · Cited by 20
Prevention of bone mineral density loss in patients with rheumatoid arthritis treated with anti-TNFα therapy
Miossec, P. (2008) · Biologics · doi:10.2147/btt.s2338 · Cited by 27
“Furthermore, TNF α stimulation also induces apoptosis in osteoblasts (Hill et al 1997; Jilka et al 1998).”
Oral malodorous compound causes caspase‐8 and ‐9 mediated programmed cell death in osteoblasts
Aoyama, I., Calenic, B., Imai, T., Hiroshi, I. I., & Yaegaki, K. (2011) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2011.01442.x · Cited by 24
Hypoxia mediates osteocyte ORP150 expression and cell death in vitro
Montesi, M., Jähn, K., Bonewald, L. F., Stea, S., Bordini, B., & Beraudi, A. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5790 · Cited by 25
“Osteocyte viability and total cell number were determined by trypan blue staining (39,40).”
Rapid new bone tissue remodeling during distraction osteogenesis is associated with apoptosis
Li, G., Dickson, G. R., Marsh, D., & Simpson, H. (2002) · Journal of Orthopaedic Research® · doi:10.1016/s0736-0266(02)00097-9 · Cited by 24
“Apoptosis is closely involved in tissue remodeling during development and repair [12,13,16,17,22,25,30].”
Background
Osteocyte Apoptosis and Absence of Bone Remodeling in Human Auditory Ossicles and Scleral Ossicles of Lower Vertebrates: A Mere Coincidence or Linked Processes?
Palumbo, C., Cavani, F., Sena, P., Benincasa, M., & Ferretti, M. (2012) · Calcified Tissue International · doi:10.1007/s00223-012-9569-6 · Cited by 22
“The importance of apoptosis in the histophysiology of skeletal tissues and, in particular, its functional relationship with bone turnover have been investigated by various authors [11–13] in order to understand whether and how the mechanism of programmed cell death interferes with bone modeling and remodeling.”
Background
HIV infection, bone metabolism, and fractures.
Güerri-Fernández, R., Villar-García, J., Diez-Perez, A., & Prieto-Alhambra, D. (2014) · Arquivos brasileiros de endocrinologia e metabologia · doi:10.1590/0004-2730000003323 · Cited by 25
Impaired Fracture Healing after Hemorrhagic Shock
Lichte, P., Kobbe, P., Pfeifer, R., Campbell, G. C., Beckmann, R., Tohidnezhad, M., Bergmann, C., Kadyrov, M., Fischer, H., Glüer, C., et al. (2015) · Mediators of Inflammation · doi:10.1155/2015/132451 · Cited by 22
“TNFα was shown to increase the serum calcium of mice [24] and to stimulate new osteoclast formation and bone resorption [25], whereas it is potently proapoptotic for osteoblasts [26].”
PTH and PTHrP Actions on Kidney and Bone
Bisello, A., & Friedman, P. A. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00050-1 · Cited by 23
The Effect of Long-Term Exercise on the Production of Osteoclastogenic and Antiosteoclastogenic Cytokines by Peripheral Blood Mononuclear Cells and on Serum Markers of Bone Metabolism
Smith, J. K., Dykes, R., & Chi, D. S. (2016) · Journal of Osteoporosis · doi:10.1155/2016/5925380 · Cited by 22
“IL-6 enhances bone formation by promoting the differentiation of osteoblast precursors [33, 34] and by protecting osteoblasts against apoptosis [5, 35]; it can inhibit bone resorption directly by downregulating RANKL signaling pathways in osteoclasts [36] and indirectly by suppressing the production of TNF-α and IL-1…”
The Growth Proliferation, Apoptotic Prevention, and Differentiation Induction of the Gelatin Hydrolysates from Three Sources to Human Fetal Osteoblasts (hFOB 1.19 Cells)
Lu, M., & Zhao, X. (2018) · Molecules · doi:10.3390/molecules23061287 · Cited by 23
“Apoptosis is also a crucial determinant of the life span of the osteoblasts in bone-forming function [28].”
Background
Long-term effects of tripeptide Ile-Pro-Pro on osteoblast differentiation in vitro
Huttunen, M. M., Pekkinen, M., Ahlström, M., & Lamberg-Allardt, C. J. E. (2008) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2007.09.006 · Cited by 22
“A reduction in osteoblast apoptosis could enhance bone formation [36].”
Background
Combined effects of dentin sialoprotein and bone morphogenetic protein-2 on differentiation in human cementoblasts
Lee, S., Auh, Q., Kang, S., Kim, H. J., Lee, J., Noh, K., Jang, J., & Kim, E.-C. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1831-y · Cited by 22
“MG63 cells (ATCC, Rockville, MD, USA) were cultured in Dulbecco’s modified Eagle’s medium (Invitrogen) containing 10 % FBS as previously described (Jilka et al. 1998).”
Method
Immunology of Gut-Bone Signaling
Collins, F. L., Schepper, J. D., Rios‐Arce, N. D., Steury, M. D., Kang, H. J., Mallin, H., Schoenherr, D. T., Camfield, G., Chishti, S., McCabe, L. R., et al. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-66653-2_5 · Cited by 22
Single-cell spatiotemporal analysis reveals cell fates and functions of transplanted mesenchymal stromal cells during bone repair
Yang, C., Li, Z., Liu, Y., Hou, R., Lin, M., Fu, L., Wu, D., Liu, Q., Li, K., & Liu, C. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.08.008 · Cited by 20
“the apoptosis of fNP-MSC-derived osteoblasts and endocytosis of cell debris by macrophages (Jilka et al., 1998).”
Background
Influences of Aged Bone Marrow Macrophages on Skeletal Health and Senescence
Pappert, M., Khosla, S., & Doolittle, M. L. (2023) · Current Osteoporosis Reports · doi:10.1007/s11914-023-00820-8 · Cited by 22
“While osteoblasts can develop into osteocytes or bone lining cells, a larger majority of osteoblasts undergo cell death [47].”
Background
Protective effect of kobophenol A on nitric oxide-induced cell apoptosis in human osteoblast-like MG-63 cells: Involvement of JNK, NF-κB and AP-1 pathways
Lee, S., Kwak, J.-H., Park, D.-S., & Pyo, S. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2011.04.004 · Cited by 20
Serum from children with polyarticular juvenile idiopathic arthritis (pJIA) inhibits differentiation, mineralization and may increase apoptosis of human osteoblasts “in vitro”
Caparbo, V. F., Prada, F. D. S., Silva, C. A., Regio, P. L., & Pereira, R. M. R. (2008) · Clinical Rheumatology · doi:10.1007/s10067-008-0985-y · Cited by 20
“Osteoblasts undergoing apoptosis can be modulated by growth factors and cytokines produced in the bone microenvironment [18].”
Background
Effects of 17β-estradiol, tamoxifen and raloxifene on the protein and mRNA expression of interleukin-6, transforming growth factor-β1 and insulin-like growth factor-1 in primary human osteoblast cultures
Méndez‐Dávila, C., García-Moreno, C., Turbí, C., & de la Piedra, C. (2004) · Journal of Endocrinological Investigation · doi:10.1007/bf03347531 · Cited by 20
RUNX2 regulates the effects of TNFα on proliferation and apoptosis in SaOs-2 cells
Ghali, O., Chauveau, C., Lencel, P., Romain, S., Khaled, H., Hardouin, P., Broux, O., & Jean-Christophe, D. (2010) · Bone · doi:10.1016/j.bone.2009.12.027 · Cited by 19
“Numerous studies support the apoptotic action of TNFα in osteoblasts [30–32].”
Potential Induction of Bone Regeneration by Nacre: An In Vitro Study
Asvanund, P., CHUNHABUNDIT, P., & Suddhasthira, T. (2011) · Implant Dentistry · doi:10.1097/id.0b013e3182061be1 · Cited by 19
Effect of progesterone on apoptosis of murine MC3T3-E1 osteoblastic cells
Wang, Q.-P., Xie, H., Yuan, L., Luo, X., Li, H., Wang, D., Meng, P., & Liao, E.-Y. (2008) · Amino Acids · doi:10.1007/s00726-008-0028-7 · Cited by 19
“Recent evidence indicates that apoptosis represents the most common fate of osteoblasts during physiologic bone remodeling (Jilka et al. 1998, 1999; Plotkin et al. 1999).”
Background
Effect of alendronate on bone mineral density in male idiopathic osteoporosis
Weber, T. J., & Drezner, M. K. (2001) · Metabolism · doi:10.1053/meta.2001.24925 · Cited by 19
The Effects of Dickkopf-4 on the Proliferation, Differentiation, and Apoptosis of Osteoblasts
Hiramitsu, S., Terauchi, M., & Kubota, T. (2013) · Endocrinology · doi:10.1210/en.2013-1387 · Cited by 18
Bisphosphonate-Associated Osteomyelitis of the Jaw: Guidelines for Practicing Clinicians
Wimalawansa, S. J. (2008) · Endocrine Practice · doi:10.4158/ep.14.9.1150 · Cited by 18
Targeting Fas in osteoresorptive disorders
Kovačić, N., Grčević, D., Katavić, V., Lukić, I. K., & Marušić, A. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.522347 · Cited by 18
“As the largest part of the cells of the skeletal system undergo apoptosis, up to 80% of osteoblasts [51], and most of osteoclasts [70], it has long been postulated that the Fas--Fas ligand system is involved in the regulation of, at least, some aspects of bone cell proliferation and cell death.”
Biologic Foundations for Skeletal Tissue Engineering
Bueno, E. M., & Glowacki, J. (2011) · Synthesis lectures on tissue engineering · doi:10.1007/978-3-031-02583-9 · Cited by 21
RSK2 protects mice against TNF-induced bone loss
Böhm, C., Derer, A., Axmann, R., Hillienhoff, U., Zaiss, M. M., Luther, J., Zech, C., Stock, M., Scholtysek, C., Engelke, K., et al. (2012) · Journal of Cell Science · doi:10.1242/jcs.096008 · Cited by 18
“This phenotype appears to be caused by an increased sensitivity of the osteoblastogenic cells to TNF-a.”
Background
New developments in IL-6 dependent biology and therapy: where do we stand and what are the options?
Kallen, K., Galle, P. R., & Rose‐John, S. (1999) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.8.9.1327 · Cited by 19
Receptors for Parathyroid Hormone (PTH) and PTH-Related Peptide
Gardella, T. J., Jüppner, H., Bringhurst, F. R., & Potts, J. T. J. (2002) · Elsevier eBooks · doi:10.1016/b978-012098652-1.50126-8 · Cited by 18
Enamel matrix derivative inhibits TNF-α–induced apoptosis in osteoblastic MC3T3-E1 cells
He, J., King, Y., Jiang, J. Q., Safavi, K. E., Spångberg, L. S. W., & Zhu, Q. (2004) · Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology · doi:10.1016/j.tripleo.2004.07.022 · Cited by 18
Osteoblast Biology
Lian, J. B., & Stein, G. S. (2001) · Elsevier eBooks · doi:10.1016/b978-012470862-4/50003-9 · Cited by 18
Adenosine Inhibition of Lipopolysaccharide-Induced Interleukin-6 Secretion by the Osteoblastic Cell Line MG-63
Russell, J. M., Stephenson, G. S., Yellowley, C. E., & Benton, H. P. (2007) · Calcified Tissue International · doi:10.1007/s00223-007-9060-y · Cited by 17
“Studies using MC3T3-E1, a mouse preosteoblast cell line, and MG-63 cells showed that treatment with an IL-6-like cytokine, murine leukemia inhibitory factor (LIF), had an antiapoptotic effect during serum starvation [43].”
Longitudinal Functional Study of Murine Aging: A Resource for Future Study Designs
Evans, D. S., O’Leary, M. N., Murphy, R. A., Schmidt, M., Koenig, K. L., Presley, M. P., Garrett, B., Kim, H., Li, H., Academia, E. C., et al. (2021) · JBMR Plus · doi:10.1002/jbm4.10466 · Cited by 16
“Calvaria cells were isolated from 3- to 4-day-old C57BL/6 mice as described.((35)) To obtain bonemarrow–derived stromal cells, total bone marrow cells pooled from 3–4 C57BL/6 female mice at 2–4 months of age were cultured with 20% FBS, 1% penicillin– streptomycin–glutamine, and 50 μg/ml of ascorbic acid (Sigma) in 10-…”
Method
Combined effect of tnf-α polymorphisms and hypoxia on steroid-induced osteonecrosis of femoral head.
Liu, Y., Jiang, W., Liu, S., Su, X., & Zhou, S. (2015) · PubMed Central · Cited by 17
Cellular Actions of Parathyroid Hormone
Kousteni, S., & Bilezikian, J. P. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00049-5 · Cited by 16
Basics of Bone Biology
Rauner, M., Stein, N., & Hofbauer, L. C. (2011) · Springer eBooks · doi:10.1007/978-3-7091-0520-7_1 · Cited by 16
Identification of C‐terminal Hsp70‐interacting protein as a mediator of tumour necrosis factor action in osteoblast differentiation by targeting osterix for degradation
Xie, J., & Gu, J. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12553 · Cited by 16
Transforming growth factor-β3 relation with osteoporosis and osteoporotic fractures
Haghighizadeh, E., Shahrezaee, M., Sharifzadeh, S. R., & Momeni, M. (2019) · Journal of Research in Medical Sciences · doi:10.4103/jrms.jrms_1062_18 · Cited by 16
“Positive survival effect of different types of TGF‑β on cultured osteoblast‑lineage cells was approved by Dufour et al.,[12] Karsdal et al.[13] and Jilka et al.[14] The effect of TGF‑β3 on osteocytes and osteoblasts may be more potent than TGF‑β1 or TGF‑β2.”
Upregulated expression of inducible nitric oxide synthase plays a key role in early apoptosis after anterior cruciate ligament injury
Murakami, H., Shinomiya, N., Kikuchi, T., Yoshihara, Y., & Nemoto, K. (2006) · Journal of Orthopaedic Research® · doi:10.1002/jor.20151 · Cited by 16
Differential sensitivity to NO-induced apoptosis between anterior cruciate and medial collateral ligament cells
Murakami, H., Shinomiya, N., Kikuchi, T., Fujikawa, K., & Nemoto, K. (2005) · Journal of Orthopaedic Science · doi:10.1007/s00776-004-0858-4 · Cited by 16
Dexamethasone Suppresses Tumor Necrosis Factor- -Induced Apoptosis in Osteoblasts: Possible Role for Ceramide
Chae, H. (2000) · Endocrinology · doi:10.1210/en.141.8.2904 · Cited by 16
Closing cones create conical lamellae in secondary osteonal bone
Doube, M. (2022) · Royal Society Open Science · doi:10.1098/rsos.220712 · Cited by 13
“Three fates for osteoblasts are recognized: half or more undergo apoptosis [35], with the remainder burying themselves in osteoid and differentiating into long-lived osteocytes [36,37] or differentiating into senescent, flattened bone lining cells covering the Haversian canal surface.”
Background
Efferocytosis and Bone Dynamics
Batoon, L., Hawse, J. R., McCauley, L. K., Weivoda, M. M., & Roca, H. (2024) · Current Osteoporosis Reports · doi:10.1007/s11914-024-00878-y · Cited by 16
“Osteoblasts have three main fates, including differentiation into bone-lining cells or bone-embedded osteocytes, or as is the case for the majority of osteoblasts, undergo apoptosis [63].”
Inhibiting effect of microRNA-187-3p on osteogenic differentiation of osteoblast precursor cells by suppressing cannabinoid receptor type 2
Xu, A., Yang, Y., Shao, Y., Wu, M., & Sun, Y. (2019) · Differentiation · doi:10.1016/j.diff.2019.07.002 · Cited by 15
Effects of Tunicamycin, Mannosamine, and Other Inhibitors of Glycoprotein Processing on Skeletal Alkaline Phosphatase in Human Osteoblast-Like Cells
Farley, J. R., & Magnusson, P. (2004) · Calcified Tissue International · doi:10.1007/s00223-004-0023-2 · Cited by 15
Epigallocatechin-3-gallate protects against tumor necrosis factor alpha induced inhibition of osteogenesis of mesenchymal stem cells
Liu, W. X., Fan, J., Xu, D., Zhang, J., & Cui, Z. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370215624020 · Cited by 15
Review of “Universal” Rules Governing Bone Composition, Organization, and Elasticity Across Organizational Hierarchies
Vass, V., Morin, C., Scheiner, S., & Hellmich, C. (2017) · Courses and lectures · doi:10.1007/978-3-319-58845-2_4 · Cited by 15
Traf2 interacts with Smad4 and regulates BMP signaling pathway in MC3T3-E1 osteoblasts
Shimada, K., Ikeda, K., & Ito, K. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.10.048 · Cited by 14
Cellular Actions of PTH
Silva, B. C. C., & Kousteni, S. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397166-1.00008-4 · Cited by 15
Kobophenol A enhances proliferation of human osteoblast-like cells with activation of the p38 pathway
Kwak, J.-H., Lee, S.-R., Park, H.-J., Byun, H.-E., Sohn, E., Kim, B.-O., Rhee, D., & Pyo, S. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.08.015 · Cited by 14
Local Regulators of Bone
Horowitz, M. C., & Lorenzo, J. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00071-9 · Cited by 14
Toll-Like Receptor Stimulation Induces Higher TNF-α Secretion in Peripheral Blood Mononuclear Cells from Patients with Hyper IgE Syndrome
Yeganeh, M., Henneke, P., Rezaei, N., Ehl, S. R., Thiel, D., Matamoros, N., Pietrogrande, C., Español, T., Litzman, J., Franco, J. L., et al. (2008) · International Archives of Allergy and Immunology · doi:10.1159/000115886 · Cited by 14
The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease
Bishop, R. T., Miller, A. K., Froid, M., Nerlakanti, N., Li, T., Frieling, J. S., Nasr, M. M., Nyman, K. J., Sudalagunta, P. R., Canevarolo, R. R., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46594-0 · Cited by 16
“We assume that the amount of bone that osteoclasts resorb is proportional to their lifespan of approximately 14 days 86,101 .”
Cell life-or-death events in osteoporosis: All roads lead to mitochondrial dynamics
Li, Z., Liang, S., Ke, L., Wang, M., Gao, K., Li, D., Xu, Z., Li, N., Zhang, P., & Cheng, W. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107383 · Cited by 14
The relationship between pro-resorptive inflammatory cytokines and the effect of high dose vitamin D supplementation on their circulating concentrations
Karim, M. Y., Turner, C., Dalton, N. R., Roplekar, R., Sankaralingam, A., Ewang, M., Fogelman, I., & Hampson, G. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.08.010 · Cited by 14
PTH1 Receptor Is Involved in Mediating Cellular Response to Long-Chain Polyunsaturated Fatty Acids
Candelario, J., Tavakoli, H., & Chachisvilis, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052583 · Cited by 13
“TUNEL staining [61] with at least 90% of trypan blue-stained”
Method
Megakaryocyte Secreted Factors Regulate Bone Marrow Niche Cells During Skeletal Homeostasis, Aging, and Disease
Karnik, S. J., Nazzal, M. K., Kacena, M. A., & Bruzzaniti, A. (2023) · Calcified Tissue International · doi:10.1007/s00223-023-01095-y · Cited by 12
“TGFβ1 promotes OB proliferation and DNA damage repair while simultaneously inhibiting OB apoptosis [58, 62].”
Background
Ultrastructural changes during osteogenic differentiation in mesenchymal stromal cells cultured in alginate hydrogel
Grzesiak, J., Śmieszek, A., & Marycz, K. (2017) · Cell & Bioscience · doi:10.1186/s13578-016-0128-0 · Cited by 12
“described, that the number of osteoblasts in the bone growth zone is not equal to the number of cells present in this area after the tissue development is finished, which suggests that some part of cells undergo cellular death [17].”
Matrix metalloproteinase processing of PTHrP yields a selective regulator of osteogenesis, PTHrP1–17
Frieling, J. S., Shay, G., Izumi, V., Aherne, S. T., Saul, R. G., Budzevich, M. M., Koomen, J. M., & Lynch, C. C. (2017) · Oncogene · doi:10.1038/onc.2017.70 · Cited by 12
Conditional Loss of Nmp4 in Mesenchymal Stem Progenitor Cells Enhances PTH-Induced Bone Formation
Atkinson, E. G., Adaway, M., Horan, D. J., Korff, C., Klunk, A. J., Orr, A. L., Ratz, K., Bellido, T., Plotkin, L. I., Robling, A. G., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4732 · Cited by 13
“) Furthermore, not all mature osteoblasts, ie, Bglap-expressing cells, give rise to osteocytes; some become bone lining cells and some are lost to apoptosis.((92,97,98)) Therefore, the architecture of the Nmp4 / osteocyte lacunocanalicular network may differ between the Nmp4;BglapCre and Nmp4;Dmp1Cre mice.”
BackgroundSelf-citation
Antiapoptotic molecule Bcl‐2 is essential for the anabolic activity of parathyroid hormone in bone
Nagase, Y., Iwasawa, M., Akiyama, T., Ogata, N., Kadono, Y., Nakamura, M., Oshima, Y., Yasui, T., Matsumoto, T., Masuda, H., et al. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05209.x · Cited by 12
Biomimetic materials for controlling bone cell responses
Drevelle, O. (2012) · Frontiers in Bioscience-Scholar · doi:10.2741/s378 · Cited by 12
“Thus 50-70% of the osteoblasts involved in active BMU in human bone remodeling die during the terminal phase (22,111).”
Background
The Cooperative Effect of Genistein and Protein Hydrolysates on the Proliferation and Survival of Osteoblastic Cells (hFOB 1.19)
Wang, S., Fu, Y., & Zhao, X. (2016) · Molecules · doi:10.3390/molecules21111489 · Cited by 12
“Apoptosis is a crucial determinant of the life span of the osteoblasts in bone-forming function [53].”
Background
Endogenous PKIγ Limits the Duration of the Anti-Apoptotic Effects of PTH and β-Adrenergic Agonists in Osteoblasts
Chen, X., Song, I., Dennis, J. E., & Greenfield, E. M. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070122 · Cited by 12
“PTH decreases osteoblast apoptosis in vivo,((3,10,11)) in osteoblast primary cultures,((3,11)) and in many osteoblastic cell lines, including OB-6 cells,((3)) MC3T3-E1 cells, UMR 106 cells,((13)) MG-63 cells,((11,37)) MLO-Y4 cells,((11)) and C3H10T1/2 cells transfected with PTH receptors.”
BackgroundMethodInfluential
Effect of VDR gene polymorphisms on osteocalcin secretion in calcitriol-stimulated human osteoblasts
Naves‐Díaz, M., Álvarez-Hernández, D., Martín, J. L. F., Paz-Jiménez, J., García-Prado, P., Fernández‐Coto, T., Santamaría, Í., & Cannata-Andía, J. B. (2003) · Kidney International · doi:10.1046/j.1523-1755.63.s85.7.x · Cited by 12
Lifetime high calcium intake increases osteoporotic fracture risk in old age
Klompmaker, T. R. (2005) · Medical Hypotheses · doi:10.1016/j.mehy.2005.04.022 · Cited by 12
“Unfortunately, 50–70% of the composing osteoblasts die in the composition of new matrix [17], and osteoblasts have a limited proliferative capacity [18– 20].”
Cellular and Molecular Biology of Orthodontic Tooth Movement
Maltha, J. C., Krishnan, V., & Kuijpers‐Jagtman, A. M. (2021) · doi:10.1002/9781119608912.ch3 · Cited by 12
A novel lncRNA GM15416 regulates osteoblast apoptosis and differentiation through the c-Fos/Fas axis and mitigates osteoporosis
Zhao, D., He, J., Zhao, X., Sheng, X., Feng, Z., Wang, X., Zhang, C., Wang, S., Geng, B., & Xia, Y. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.127824 · Cited by 11
Stimulators of Mineralization Limit the Invasive Phenotype of Human Osteosarcoma Cells by a Mechanism Involving Impaired Invadopodia Formation
Cmoch, A., Podszywalow‐Bartnicka, P., Palczewska, M., Piwocka, K., Groves, P. D., & Pikuła, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109938 · Cited by 11
“Our results are consistent with the latest knowledge on cellular mineralization which points to apoptosis as one of the main mechanisms [38–42].”
Result
In vitro evaluation of the biological effect of SOFAT on osteoblasts
Napimoga, M. H., Demasi, A. P. D., Jarry, C. R., Ortega, M. C., de Araújo, V. C., & Martinez, E. F. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.04.033 · Cited by 11
“In addition, IL-6 is an anti-apoptotic agent for these cells [22].”
Effect of risperidone on proliferation and apoptosis of MC3T3-E1 cells
Zheng, L., Yang, L., Zhao, X., Long, N., Li, P., & Wang, Y. (2019) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20188098 · Cited by 11
“(28) found that TNF-a promoted osteoblast apoptosis in vitro, a process involved in the pathology of osteoporosis.”
Background
The Impact of Sex Hormone Changes on Bone Mineral Deficit in Chronic Renal Failure
Doumouchtsis, K., Perrea, D. N., & Doumouchtsis, S. K. (2009) · Endocrine Research · doi:10.1080/07435800903127598 · Cited by 12
Apoptosis in Bone Cells
Boyce, B. F., Xing, L., Jilka, R. L., Bellido, T., Weinstein, R. S., PARFITT, A. M., & Manolagas, S. C. (2002) · Elsevier eBooks · doi:10.1016/b978-012098652-1.50112-8 · Cited by 21
Self-citation

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

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

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks