Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling
Abstract
Expression of receptor for advanced glycation end products (RAGE) plays a crucial role in bone metabolism. However, the role of RAGE in the control of osteoblast proliferation is not yet evaluated. In the present study, we demonstrate that RAGE overexpression inhibits osteoblast proliferation in vitro. The negative regulation of RAGE on cell proliferation results from suppression of Wnt, PI3K and ERK signaling, and is restored by RAGE neutralizing antibody. Prevention of Wnt signaling using Sfrp1 or DKK1 rescues RAGE-decreased PI3K and ERK signaling and cell proliferation, indicating that the altered cell growth in RAGE overexpressing cells is in part secondary to alterations in Wnt signaling. Consistently, RAGE overexpression inhibits the expression of Wnt targets cyclin D1 and c-myc, which is partially reversed by RAGE blockade. Overall, these results suggest that RAGE inhibits osteoblast proliferation via suppression of Wnt, PI3K and ERK signaling, which provides novel mechanisms by which RAGE regulates osteoblast growth.
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The AGE-RAGE interaction augments production of proinflammatory cytokines and suppresses osteoblast differentiation via the Wnt, PI3K, and ERK1/2 signaling pathways.
“The interaction of AGE-RAGE augments the production of proinflammatory cytokines and suppresses osteoblast differentiation via the Wnt, PI3K, and ERK1/2 signaling pathways83.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [83]
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References 28 · Cited by 65
- Authors
- Li, G., Xu, J., & Li, Z.
- Affiliations
- Tongji University (CN)
- Corresponding author
- Li, Zengchun
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 423
- Issue
- 4
- Pages
- 684-689
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2000069766
- Cited by
- 65
- References
- 28
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 9 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 1
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- 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 › Wnt/β-catenin signaling in development and cancer
- Keywords
- receptor for advanced glycation end products, RAGE, osteoblast proliferation, Wnt signaling, PI3K signaling, ERK signaling, bone metabolism, SFRP1, DKK1, cyclin D1, c-Myc
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Cell Line, Osteoblasts, Receptors, Immunologic, Signal Transduction, Glycation End Products, Advanced, Phosphatidylinositol 3-Kinases, MAP Kinase Signaling System, Cell Proliferation, beta Catenin, Mice, Wnt Signaling Pathway
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