AGEs Induce Apoptosis in Rat Osteoblast Cells by Activating the Caspase-3 Signaling Pathway Under a High-Glucose Environment In Vitro
Abstract
Advanced glycation end products (AGEs) accumulate under high-glucose conditions and affect the healing of bone damage through various pathways; however, the detail mechanisms underlying these changes are unknown. In this study, we investigated the effects of AGEs on the apoptosis of in vitro-cultured rat osteoblasts under high-glucose conditions and explored the underlying mechanisms of these effects. First, we cultured rat osteoblasts and determined the accumulation of AGEs in the culture medium under high-glucose conditions. Then, we cultured rat osteoblasts under a high glucose concentration (35 mM), a normal glucose concentration (5.5 mM), and a normal glucose concentration (5.5 mM) in the presence of AGEs. We examined the effects of high glucose and AGEs on the apoptosis of rat osteoblasts at different time points and further analyzed the activity and changes in the levels of procaspase-3, caspase-3, and the caspase-3 substrate poly ADP-ribose polymerase (PARP). Finally, we added sRAGE (soluble RAGE) (an AGE inhibitor) or DEVD (a caspase-3 inhibitor) to each culture group and examined apoptosis under each culture condition and the changes in the levels of procaspase-3, caspase-3, and its substrate PARP. The results showed that the high-glucose condition and the addition of AGEs increased the apoptosis of rat osteoblast cells and simultaneously increased the activity and quantity of caspase-3. These increases could be inhibited by the AGE inhibitor sRAGE or the caspase-3 inhibitor DEVD. The above results demonstrate that high-glucose conditions lead to the accumulation of AGEs and activation of the caspase-3 signaling pathway, resulting in the increased apoptosis of cultured rat osteoblast cells.
Integrity signals
Registry
Cites
Statistics
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?
AGEs enhance levels of osterix, a transcription factor that promotes osteoblast differentiation and bone formation.
“Initially, AGEs enhance the levels of osterix, a transcription factor that promotes osteoblast differentiation and bone formation.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [81]
Chronic AGE accumulation induces osteoblast apoptosis through activation of proapoptotic caspase-3, MAPK, and intracellular ROS generation.
“However, chronic AGE accumulation induces osteoblast apoptosis through activation of proapoptotic caspase-3, MAPK, and intracellular ROS generation80–82, indicating an intricate role for AGEs in bone physiology and remodeling.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [81]
Cites
Alikhani, M., Alikhani, Z., Boyd, C. M., MacLellan, C. M., Raptis, M., Liu, R., Pischon, N., Trackman, P. C., Gerstenfeld, L. C., & Graves, D. T. (2006) · Bone · doi:10.1016/j.bone.2006.09.011 · Cited by 376 · see citing works
Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes
Satin, L. S., Butler, P. C., Ha, J., & Sherman, A. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2015.01.003 · Cited by 234 · see citing works
Ratio of Serum Levels of AGEs to Soluble Form of RAGE Is a Predictor of Endothelial Function
Kajikawa, M., Nakashima, A., Fujimura, N., Maruhashi, T., Iwamoto, Y., Iwamoto, A., Matsumoto, T., Oda, N., Hidaka, T., Kihara, Y., et al. (2014) · Diabetes Care · doi:10.2337/dc14-1435 · Cited by 104 · see citing works
Okazaki, K., Yamaguchi, T., Tanaka, K.-I., Notsu, M., Ogawa, N., Yano, S., & Sugimoto, T. (2012) · Calcified Tissue International · doi:10.1007/s00223-012-9641-2 · Cited by 98 · see citing works
Mercer, N., Ahmed, H., Etcheverry, S. B., Vasta, G. R., & Cortizo, A. M. (2007) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-007-9557-8 · Cited by 83 · see citing works
Irles, E., Ñeco, P., Lluesma, M., Villar-Pazos, S., Santos-Silva, J. C., Vettorazzi, J. F., Alonso‐Magdalena, P., Carneiro, E. M., Boschero, A. C., Nadal, Á., et al. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.01.033 · Cited by 53 · see citing works
MiR-421 Regulates Apoptosis of BGC-823 Gastric Cancer Cells by Targeting Caspase-3
Wu, J.-H., Yao, Y., Gu, T., et al. (2014) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2014.15.13.5463 · Cited by 50 · see citing works
Wu, B., Cui, J., Zhang, C., et al. (2012) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2012.02.023 · Cited by 48 · see citing works
Zhang, X., Zhao, Y., Chu, Q., et al. (2014) · Biological Trace Element Research · doi:10.1007/s12011-014-9922-x · Cited by 41 · see citing works
Bone quality and strength are greater in growing male rats fed fructose compared with glucose
Bass, E. F., Baile, C. A., Lewis, R. D., & Giraudo, S. Q. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.08.006 · Cited by 34 · see citing works
Dhanasekaran, M., Indumathi, S., Rajkumar, J. S., & Sudarsanam, D. (2012) · Cell Biochemistry and Function · doi:10.1002/cbf.2851 · Cited by 30 · see citing works
Liu, Z., Jiang, H., Dong, K., Liu, S., Zhou, W., Zhang, J., Meng, L., Rausch‐Fan, X., & Xu, X. W. (2015) · Implant Dentistry · doi:10.1097/id.0000000000000196 · Cited by 28 · see citing works
Guo, C., Zeng, X., Song, J., Zhang, M., Wang, H., Xu, X., Du, F., & Chen, B. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130911923 · Cited by 26 · see citing works
Szwed, M., Laroche‐Clary, A., Robert, J., et al. (2014) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2014.06.013 · Cited by 22 · see citing works
Liu, J., Wang, Y., Yuan, X. H., et al. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.08.013 · Cited by 16 · see citing works
Self-citationCaspase-3–mediated splenic lymphocyte apoptosis in a porcine model of cardiac arrest
Gu, W., Zhang, Q., Yin, W., et al. (2014) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2014.06.004 · Cited by 15 · see citing works
Wang, R., Wang, R., Liang, H., et al. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.03.064 · Cited by 12 · see citing works
Węsierska‐Gądek, J., & Heinzl, S. (2014) · Journal of Cancer Prevention · doi:10.15430/jcp.2014.19.2.125 · Cited by 6 · see citing works
Ruzicska, É., & Poór, G. (2011) · Orvosi Hetilap · doi:10.1556/oh.2011.29147 · Cited by 4 · see citing works
Ferrucci, A., Leboffe, L., Agamennone, M., et al. (2014) · Amino Acids · doi:10.1007/s00726-014-1855-3 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rungratanawanich, W., Qu, Y., Wang, X., Essa, M. M., & Song, B.-J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00561-7 · Cited by 411 · see citing works
RAGE Signaling in Skeletal Biology
Plotkin, L. I., Essex, A. L., & Davis, H. M. (2019) · Current Osteoporosis Reports · doi:10.1007/s11914-019-00499-w · Cited by 54 · see citing works
Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions
Donat, A., Knapstein, P.-R., Jiang, S., Baranowsky, A., Ballhause, T.-M., Frosch, K.-H., & Keller, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084120 · Cited by 53 · see citing works
- Authors
- Liu, J., Mao, J., Jiang, Y., Xia, L., Mao, L., Wu, Y., Ma, P., & Fang, B.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Shanghai First Maternity and Infant Hospital (CN)
- Chinese PLA General Hospital (CN)
- Capital Medical University (CN)
- Corresponding author
- Fang, Bing
- Venue
- Applied Biochemistry and Biotechnology
- Published
- 2015-11-14
- Volume
- 178
- Issue
- 5
- Pages
- 1015-1027
- ISSN
- 0273-2289 (ISSN-L)
- 1559-0291
- OpenAlex
- W2174310885
- Cited by
- 30
- References
- 20
- Citations by year
- 2026: 3 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 8 · 2020: 1 · 2019: 6 · 2018: 1 · 2017: 3 · 2016: 2
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Applied Biochemistry and Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of China (No.81371178)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- 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
- Keywords
- advanced glycation end products, osteoblast apoptosis, caspase-3, high glucose, soluble RAGE, PARP cleavage, diabetic bone disease
- MeSH terms
- Animals, Cells, Cultured, Glucose, Osteoblasts, Signal Transduction, Glycation End Products, Advanced, Apoptosis, Rats, Caspase 3
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
