APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age-dependent manner
Open accessAbstract
Alzheimer's disease (AD), one of the most dreaded neurodegenerative disorders, is characterized by cortical and cerebrovascular amyloid β peptide (Aβ) deposits, neurofibrillary tangles, chronic inflammation, and neuronal loss. Increased bone fracture rates and reduced bone density are commonly observed in patients with AD, suggesting one or more common denominators between both disorders. However, very few studies are available that have addressed this issue. Here, we present evidence for a function of amyloid precursor protein (APP) and Aβ in regulating osteoclast (OC) differentiation in vitro and in vivo. Tg2576 mice, which express the Swedish mutation of APP (APPswe) under the control of a prion promoter,1,2 exhibit biphasic effects on OC activation, with an increase of OCs in younger mice (< 4 months old), but a decrease in older Tg2576 mice (> 4 months old). The increase of OCs in young Tg2576 mice appears to be mediated by Aβ oligomers and receptor for advanced glycation end products (RAGE) expression in bone marrow macrophages (BMMs). However, the decrease of OC formation and activity in older Tg2576 mice may be due to the increase of soluble rage (sRAGE) in aged Tg2576 mice, an inhibitor of RANKL-induced osteoclastogenesis. These results suggest an unexpected function of APPswe/Aβ, reveal a mechanism underlying altered bone remodeling in AD patients, and implicate APP/Aβ and RAGE as common denominators for both AD and osteoporosis. © 2011 American Society for Bone and Mineral Research.
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Previous studies have shown abundant APP protein expression in bone and bone marrow cells, such as macrophages, osteoclasts and osteoblasts in WT mice.
“Previous studies have shown abundant APP protein expression in bone and bone marrow cells, such as macrophages, osteoclasts and osteoblasts in WT mice79,80.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [80]
The Results section (“Age-dependent regulation of OC activation and bone mass in Tg2576 mice”; page unavailable) reports APP expression in bone marrow macrophages and osteoclasts derived from wild-type mice. It does not establish APP protein expression in osteoblasts, so the full list of cell types is not supported by this paper. (LLM, conf=0.88)
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Cites
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
RAGE Mediates a Novel Proinflammatory Axis
Hofmann, M. A., Drury, S., Fu, C., Qu, W., Taguchi, A., Lu, Y., Avila, C., Kambham, N., Bierhaus, A., Nawroth, P., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80801-6 · Cited by 1,864 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodRAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain
Deane, R., Du Yan, S., Submamaryan, R. K., LaRue, B., Jovanovic, S., Hogg, E., Welch, D., Manness, L., Lin, C., Yu, J., et al. (2003) · Nature Medicine · doi:10.1038/nm890 · Cited by 1,426 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodBlockade of RAGE-amphoterin signalling suppresses tumour growth and metastases
Taguchi, A., Blood, D. C., del Toro, G., Canet, A., Lee, D. C., Qu, W., Tanji, N., Lu, Y., Lalla, E., Fu, C., et al. (2000) · Nature · doi:10.1038/35012626 · Cited by 1,217 · see citing works
Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts.
McHugh, K. P., Hodivala-Dilke, K., Zheng, M., Namba, N., Lam, J. D., Novack, D., Feng, X., Ross, F., Hynes, R. O., & Teitelbaum, S. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8905 · Cited by 786 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
MethodSelf-citationThe redox chemistry of the Alzheimer's disease amyloid β peptide
Smith, D. G., Cappai, R., & Barnham, K. J. (2007) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.02.002 · Cited by 608 · see citing works
Bace1 modulates myelination in the central and peripheral nervous system
Hu, X., Hicks, C. W., He, W., Wong, P., Macklin, W. B., Trapp, B. D., & Yan, R. (2006) · Nature Neuroscience · doi:10.1038/nn1797 · Cited by 608 · cited 2× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
MethodSelf-citationThe Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins
Chavakis, T., Bierhaus, A., Al‐Fakhri, N., Schneider, D., Witte, S., Linn, T., Nagashima, M., Morser, J., Arnold, B., Preissner, K. T., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030800 · Cited by 583 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodRaucci, A., Cugusi, S., Antonelli, A., Barabino, S. M. L., Monti, L. D., Bierhaus, A., Reiß, K., Säftig, P., & Bianchi, M. E. (2008) · The FASEB Journal · doi:10.1096/fj.08-109033 · Cited by 560 · cited 5× · see citing works
“First, how does APPswe cause an increase of sRAGE, but a decrease of full-length RAGE? RAGE RNA splicing and protein shedding may both be involved, a possibility supported by our RT-PCR analysis of mRNA transcripts and Western blot analysis of the BMM or HEK293 culture medium that contains the extracellular domain of…”
BackgroundMethodResultInfluentialHsiao, K., Borchelt, D., Olson, K., Johannsdottir, R., Kitt, C. A., Yunis, W. S., Xu, S., Eckman, C., Younkin, S. G., Price, D., et al. (1995) · Neuron · doi:10.1016/0896-6273(95)90107-8 · Cited by 519 · cited 4× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodInfluentialBlockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice.
Lalla, E., Lamster, I., Feit, M., Huang, L., Spessot, A., Qu, W., Kislinger, T., Lu, Y., Stern, D. M., & Schmidt, A. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8942 · Cited by 362 · cited 1× · see citing works
“10), in agreement with the observation that sRAGE suppresses periodontitis-associated bone loss in diabetic mice.((44)) In addition to sRAGE, other factors, such as OPG, a well known inhibitor of RANKL, may also play a crucial role in the decrease of OCs in aged Tg2576 mice (Fig.”
Miyata, T., Hori, O., Zhang, J., Yan, S. S., Ferran, L., Iida, Y., & Schmidt, A. M. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118889 · Cited by 278 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
MethodStructural and functional insights into RAGE activation by multimeric S100B
Ostendorp, T., Leclerc, E., Galichet, A., Koch, M., Demling, N., Weigle, B., Heizmann, C., Kroneck, P., & Fritz, G. (2007) · EMBO Journal · doi:10.1038/sj.emboj.7601805 · Cited by 257 · cited 2× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
MethodStructural Basis for Pattern Recognition by the Receptor for Advanced Glycation End Products (RAGE)
Xie, J., Reverdatto, S., Frolov, A., Hoffmann, R., Burz, D. S., & Shekhtman, A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801622200 · Cited by 252 · cited 2× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
MethodThe Role of APP Processing and Trafficking Pathways in the Formation of Amyloid β‐Proteina
Selkoe, D. J., Yamazaki, T., Citron, M., Podlisny, M. B., Koo, E. H., Teplow, D. B., & Haass, C. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34401.x · Cited by 246 · see citing works
Learning and Memory in Transgenic Mice Modeling Alzheimer's Disease
Ashe, K. H. (2001) · Learning & Memory · doi:10.1101/lm.43701 · Cited by 224 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodWalsh, D. M., Klyubin, I., Shankar, G. M., Townsend, M., Fadeeva, J. V., Betts, V., Podlisny, M. B., Cleary, J. P., Ashe, K. H., Rowan, M. J., et al. (2005) · Biochemical Society Transactions · doi:10.1042/bst20051087 · Cited by 220 · cited 8× · see citing works
“Ab increase of OC formation is dependent on Ab oligomerization and RAGE It is believed that the soluble Ab oligomer, but the not monomer, is a major neurotoxic agent in the pathogenesis of AD.”
BackgroundMethodInfluentialHung, L. W., Ciccotosto, G. D., Giannakis, E., Tew, D. J., Perez, K., Masters, C. L., Cappai, R., Wade, J. D., & Barnham, K. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3916-08.2008 · Cited by 210 · see citing works
Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves
Hu, X., He, W.-X., Diaconu, C., Tang, X., Kidd, G., Macklin, W., Trapp, B. D., & Yan, R. (2008) · The FASEB Journal · doi:10.1096/fj.08-106666 · Cited by 199 · cited 2× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
MethodSelf-citationRAGE and Alzheimer's Disease: A Progression Factor for Amyloid-β-Induced Cellular Perturbation?
Yan, S. D., Bierhaus, A., Nawroth, P. P., & Stern, D. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1030 · Cited by 179 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodRegulation of osteoclast function and bone mass by RAGE
Zhou, Z., Immel, D., Xi, C.-X., Bierhaus, A., Feng, X., Mei, L., Nawroth, P., Stern, D. M., & Xiong, W.-C. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051947 · Cited by 178 · cited 10× · see citing works
“These results suggest an important role for RAGE in regulating OC maturation and activation in vitro and in vivo.((27)) We thus have further investigated functions of RAGE ligands in OC differentiation and activation and have demonstrated that HMGB1, a proinflammatory cytokine released from activated macrophages, prom…”
BackgroundMethodInfluentialSelf-citationSchmidt, A., & Stern, D. (2000) · Trends in endocrinology and metabolism · doi:10.1016/s1043-2760(00)00311-8 · Cited by 173 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodBiogenesis and metabolism of Alzheimer’s disease Aβ amyloid peptides
Evin, G. M., & Weidemann, A. (2002) · Peptides · doi:10.1016/s0196-9781(02)00063-3 · Cited by 170 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
MethodFracture Risk in Patients with Alzheimer's Disease
Melton, L. J., Beard, C. M., Kokmen, E., Atkinson, E. J., & O’Fallon, W. M. (1994) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1994.tb06859.x · Cited by 167 · cited 10× · see citing works
“Using Tg2576 mice, a well-studied animal model for AD, we showed altered OC differentiation and activity in vivo.”
BackgroundMethodInfluentialBACE1 Deficiency Causes Altered Neuronal Activity and Neurodegeneration
Hu, X., Zhou, X., He, W., Yang, J., Xiong, W., Wong, P., Wilson, C. G., & Yan, R. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1334-10.2010 · Cited by 162 · cited 2× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
MethodSelf-citationHMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE
Zhou, Z., Han, J.-Y., Xi, C.-X., Xie, J.-X., Feng, X., Wang, C.-Y., Mei, L., & Xiong, W.-C. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080234 · Cited by 160 · cited 5× · see citing works
“We thus have further investigated functions of RAGE ligands in OC differentiation and activation and have demonstrated that HMGB1, a proinflammatory cytokine released from activated macrophages, promotes RANKL-induced OC differentiation in a RAGE-dependent manner.((28)) The RAGE ligands AGE and S100 are also found to…”
BackgroundMethodInfluentialSelf-citationCheng, C., Tsuneyama, K., Kominami, R., Shinohara, H., Sakurai, S., Yonekura, H., Watanabe, T., Takano, Y., Yamamoto, H., & Yamamoto, Y. (2005) · Modern Pathology · doi:10.1038/modpathol.3800450 · Cited by 153 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodLi, W., Li, J.-H., Ashok, M., Wu, R.-Q., Chen, D., Yang, L.-H., Yang, H., Tracey, K., Wang, P., Sama, A., et al. (2007) · Journal of Immunology · doi:10.4049/jimmunol.178.6.3856 · Cited by 151 · cited 7× · see citing works
“Ab increase of OC formation is dependent on Ab oligomerization and RAGE It is believed that the soluble Ab oligomer, but the not monomer, is a major neurotoxic agent in the pathogenesis of AD.”
BackgroundMethodInfluentialRecombinant HMGB1 with cytokine-stimulating activity.
Li, J.-H., Wang, H., Mason, J. M., Levine, J., Yu, M., Ulloa, L., Czura, C., Tracey, K., & Yang, H. (2004) · JIM - Journal of Immunological Methods · doi:10.1016/j.jim.2004.04.019 · Cited by 142 · see citing works
Site-Specific Blockade of RAGE-V<sub>d</sub>Prevents Amyloid-β Oligomer Neurotoxicity
Sturchler, E., Galichet, A., Weibel, M., Leclerc, E., & Heizmann, C. W. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4878-07.2008 · Cited by 136 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodCholesterol in Alzheimers Disease: Unresolved Questions
Stefani, M., & Liguri, G. (2009) · Current Alzheimer Research · doi:10.2174/156720509787313899 · Cited by 134 · cited 4× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodInfluentialAlternative splicing of the murine receptor for advanced glycation end‐products (RAGE) gene
Kalea, A. Z., Reiniger, N., Yang, H., Arriero, M., Schmidt, A. M., & Hudson, B. I. (2009) · The FASEB Journal · doi:10.1096/fj.08-117739 · Cited by 116 · cited 4× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodInfluentialMouse Models of Alzheimer's Disease: Insight into Treatment
German, D., & Eisch, A. (2004) · Reviews in the Neurosciences · doi:10.1515/revneuro.2004.15.5.353 · Cited by 116 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodEvidence for altered LRP/RAGE expression in Alzheimer lesion pathogenesis.
Jeynes, B., & Provias, J. (2008) · Current Alzheimer Research · doi:10.2174/156720508785908937 · Cited by 99 · cited 2× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
MethodCortizo, A., Lettieri, M. G., Barrio, D., Mercer, N., Etcheverry, S., & McCarthy, A. D. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/a:1024934008982 · Cited by 88 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodRockenstein, E. M., Crews, L. A., & Masliah, E. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.08.013 · Cited by 79 · cited 4× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodInfluentialRAGE-AB Interactions in the Pathophysiology of Alzheimer's Disease
Yan, S.-D., Stern, D., Kane, M. D., Kuo, Y.-M., Lampert, H., & Roher, A. (1998) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-1998-00033 · Cited by 64 · see citing works
Blood biomarkers of osteoporosis in mild cognitive impairment and Alzheimer’s disease
Luckhaus, C., Mahabadi, B., Grass‐Kapanke, B., Jänner, M., Willenberg, H. S., Jäger, M., Supprian, T., & Fehsel, K. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0241-x · Cited by 61 · cited 1× · see citing works
“(45,46) Moreover, we also speculate that the reduced BMM cell density in aged mouse bone marrow may cause APPswe-BMMs to be insensitive to RANKL, another mechanism underlying the decrease of OCs in aged Tg2576 mice.”
BackgroundV domain of RAGE interacts with AGEs on prostate carcinoma cells
Allmen, E. U., Koch, M., Fritz, G., & Legler, D. F. (2008) · The Prostate · doi:10.1002/pros.20736 · Cited by 55 · see citing works
Upregulation of RAGE at the blood‐brain barrier in streptozotocin‐induced diabetic mice
Liu, L. P., Hong, H., Liao, J. M., Wang, T. S., Wu, J., Chen, S. S., Li, Y. Q., Long, Y., & Xia, Y. Z. (2009) · Synapse · doi:10.1002/syn.20644 · Cited by 44 · see citing works
Plasma osteoprotegerin as a biochemical marker for vascular dementia and Alzheimer's disease.
Emanuele, E., Peros, E., Scioli, G., D'Angelo, A., Olivieri, C., Montagna, L., & Geroldi, D. (2004) · International Journal of Molecular Medicine · doi:10.3892/ijmm.13.6.849 · Cited by 33 · cited 1× · see citing works
“(45,46) Moreover, we also speculate that the reduced BMM cell density in aged mouse bone marrow may cause APPswe-BMMs to be insensitive to RANKL, another mechanism underlying the decrease of OCs in aged Tg2576 mice.”
BackgroundYoshida, T., Flegler, A. J., Kozlov, A., & Stern, P. H. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22192 · Cited by 32 · cited 3× · see citing works
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethodSommerfeldt, D., Mcleod, K. J., Rubin, C. T., & Hadjiargyrou, M. (2001) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1006/bbrc.2001.5198 · Cited by 20 · cited 3×
“Human Ab (1-42) (from AnaSpec, Fremont, CA, USA) was used.”
BackgroundMethod
Flagged first, then by citations
6 of the 49 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- [3]Yankner BA Lu T 2008 Amyloid beta -protein toxicity and the pathogenesis of Alzheimer’s disease J Biol Chem PMC2643502 18957434
- [4]Tysiewicz-Dudek M Pietraszkiewicz F Drozdzowska B 2008 Alzheimer’s disease and osteoporosis: common risk factors or one condition predisposing to the other? Ortop Traumatol Rehabil 10 4 315 23 18779764
- [37]Du Yan S Zhu H Fu J Yan SF Roher A Tourtellotte WW Rajavashisth T Chen X Godman GC Stern D Schmidt AM 1997 Amyloid-beta peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease Proc Natl Acad Sci U S A 94 10 5296 301 9144231 PMC24672
- [38]Sturchler E Galichet A Weibel M Leclerc E Heizmann CW 2008 Site-specific blockade of RAGE-Vd prevents amyloid-beta oligomer neurotoxicity J Neurosci 28 20 5149 58 18480271 PMC6670634
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Jia, L., Piña-Crespo, J., & Li, Y. (2019) · Molecular Brain · doi:10.1186/s13041-019-0525-5 · Cited by 288 · see citing works
Asadipooya, K., & Uy, E. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00160 · Cited by 210 · see citing works
Vitamin D: calcium and bone homeostasis during evolution.
Bouillon, R., & Suda, T. (2014) · BoneKEy Reports · doi:10.1038/bonekey.2013.214 · Cited by 184 · see citing works
Diabetes, Collagen, and Bone Quality
Saito, M., Kida, Y., Kato, S., & Marumo, K. (2014) · Current Osteoporosis Reports · doi:10.1007/s11914-014-0202-7 · Cited by 149 · see citing works
Ginaldi, L., & Martinis, M. D. (2016) · Current Medicinal Chemistry · doi:10.2174/0929867323666160907162546 · Cited by 109 · see citing works
The Role of Ca2+-NFATc1 Signaling and Its Modulation on Osteoclastogenesis
Kang, J. Y., Kang, N., Yang, Y., Hong, J. H., & Shin, D. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103646 · Cited by 96 · see citing works
Amyloid beta peptide is elevated in osteoporotic bone tissues and enhances osteoclast function.
Li, S.-F., Liu, B., Zhang, L.-M., & Rong, L. (2014) · Bone · doi:10.1016/j.bone.2014.01.010 · Cited by 95 · see citing works
Pathophysiology of Bone Fragility in Patients with Diabetes
Palermo, A., D'Onofrio, L., Buzzetti, R., Manfrini, S., & Napoli, N. (2017) · Calcified Tissue International · doi:10.1007/s00223-016-0226-3 · Cited by 94 · see citing works
Prantner, D., Nallar, S., & Vogel, S. N. (2020) · The FASEB Journal · doi:10.1096/fj.202002136r · Cited by 92 · see citing works
Saito, M., & Marumo, K. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00072 · Cited by 88 · see citing works
“…types of AGEs such as carboxymethyllysine (CML) as well as cross-linking type of AGEs deteriorate osteoblastic function (Mercer et al., 2007; Ogawa et al., 2007) via the interaction with the cell surface receptor of AGEs, RAGE (Cortizo et al., 2003; Cui et al., 2011; Li et al., 2012).”
BackgroundXia, W.-F., Jung, J.-U., Cui, S., Xiong, S., Xiong, L., Shi, X., Mei, L., & Xiong, W. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1954 · Cited by 89 · see citing works
“5 at higher levels in younger ages and is ubiquitously expressed in multiple types of cells, including OB‐lineage and OC‐lineage cells.((20,24)) By contrast, APPswe expression in TgAPPswe‐Ocn mice is under the control of the osteocalcin promoter, which drives APPswe expression selectively in mature OB‐lineage cells in…”
BackgroundMethodResultInfluentialSelf-citationEffects of Neurological Disorders on Bone Health
Kelly, R. R., Sidles, S. J., & LaRue, A. C. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.612366 · Cited by 91 · see citing works
Alzheimer's disease and osteoporosis
Lo, R. Y., & Chen, Y. (2017) · Tzu Chi Medical Journal · doi:10.4103/tcmj.tcmj_54_17 · Cited by 68 · see citing works
“Both in vitro and in vivo examinations showed enhanced Aβ expression in bone, together with increased adipose tissue formation in the marrow space, analogous to osteoporotic bones [31,32].”
BackgroundReview: The genetics of A lzheimer's disease; putting flesh on the bones
Medway, C., & Morgan, K. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12101 · Cited by 66 · see citing works
Cornelius, C., Koverech, G., Crupi, R., Paola, R. D., Koverech, A., Lodato, F., Scuto, M., Salinaro, A., Cuzzocrea, S., Calabrese, E., et al. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00120 · Cited by 70 · see citing works
“For example, preclinical studies in the areas of anxiolytic drugs (Calabrese, 2008b), anti-seizure drugs (Calabrese, 2008e), memory enhancing agents (Calabrese, 2008a), drugs treating osteoporosis (Calabrese, 2008c), and others typically demonstrate hormetic dose responses.”
BackgroundDengler-Crish, C. M., Smith, M. A., & Wilson, G. N. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-160658 · Cited by 61 · see citing works
“Keywords: Alzheimer’s disease, bone density, microtubule-associated protein, serotonin, tau proteins, tauopathies”
Pan, J.-X., Tang, F., Xiong, F., Xiong, L., Zeng, P., Wang, B., Zhao, K., Guo, H., Shun, C., Xia, W.-F., et al. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-1123-7 · Cited by 59 · see citing works
Self-citationDengler-Crish, C. M., Ball, H. C., Lin, L., Novak, K. M., & Cooper, L. N. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.03.021 · Cited by 58 · see citing works
Erythrocyte membrane-coated nanocarriers modified by TGN for Alzheimer's disease.
Gu, J., Yan, C., Yin, S., Wu, H., Liu, C., Xue, A., Lei, X., Zhang, N., & Geng, F. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.12.030 · Cited by 57 · see citing works
Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells.
Li, Z., Li, C.-H., Zhou, Y., Chen, W.-S., Luo, G.-T., Zhang, Z.-J., Wang, H.-X., Zhang, Y.-C., Xu, D.-L., & Sheng, P. (2016) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00309.2015 · Cited by 54 · see citing works
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Therapeutic potential of iron chelators on osteoporosis and their cellular mechanisms
Zhang, J., Zhao, H., Yao, G., Qiao, P., Li, L., & Wu, S. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111380 · Cited by 56 · see citing works
Yang, B., Li, S.-F., Chen, Z., Feng, F., He, L., Liu, B., He, T., Wang, X., Chen, R.-Q., Chen, Z.-H., et al. (2020) · The FASEB Journal · doi:10.1096/fj.201901550r · Cited by 49 · see citing works
Li, S.-F., Yang, B., Teguh, D., Zhou, L., Xu, J.-K., & Rong, L. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101683 · Cited by 49 · see citing works
“RAGE is a member of the immunoglobulin superfamily with multiple ligands, which is crucial for the pathogenesis of diverse disorders [20,21] in Tg2576 mice [8,9], leading to the convergence of αγβ3 integrin- and M-CSF-mediated signals including activation of Rac, PYK2, Src, ERK, and c-Fos.”
BackgroundXia, W.-F., Tang, F.-L., Xiong, L., Xiong, S., Jung, J.-U., Lee, D., Li, X.-S., Feng, X., Mei, L., & Xiong, W.-C. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201207154 · Cited by 48 · see citing works
“Measurements of serum levels of osteocalcin, PYD, and IL-6 Mouse serum samples were collected and subjected to RIA analysis of PYD and ELISA analyses of IL-6 and osteocalcin as described previously (Zhou et al., 2006; Cui et al., 2011).”
MethodInfluentialSelf-citationNew advances in brain-targeting nano-drug delivery systems for Alzheimer's disease
Ouyang, Q., Meng, Y., Zhou, W., Tong, J., Cheng, Z., & Zhu, Q. (2021) · Journal of drug targeting · doi:10.1080/1061186x.2021.1927055 · Cited by 79 · see citing works
Park, Y. H., Hodges, A., Risacher, S. L., Lin, K., Jang, J., Ahn, S., Kim, S., Lovestone, S., Simmons, A., Weiner, M. W., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.12.001 · Cited by 53 · see citing works
Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives
Liu, Z., Liu, M., Xiong, Y., Wang, Y., & Bu, X. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13864 · Cited by 39 · see citing works
Xiong, F., Leonov, S. V., Howard, A. C., Xiong, S., Zhang, B., Mei, L., McNeil, P. L., Simon, S., & Xiong, W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.261073 · Cited by 37 · see citing works
Self-citationTeissier, T., Temkin, V., Pollak, R. D., & Cox, L. S. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.812157 · Cited by 35 · see citing works
“In a murine model of Alzheimer’s disease (Tg2576), aggregation of amyloid peptide precursors had a biphasic effect— increased osteoclast number and activity, and concomitant decreased trabecular volume was observed in young mice, while the opposite was seen in mice older than 6 months (Cui et al., 2011).”
BackgroundXi, H.-R., Ma, H.-P., Yang, F.-F., Gao, Y.-H., Zhou, J., Wang, Y.-Y., Li, W.-Y., Xian, C. J., & Chen, K.-M. (2018) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2018.05.023 · Cited by 33 · see citing works
Fontcuberta-Rigo, M., Nakamura, M., & Puigbò, P. (2023) · bioRxiv · doi:10.1038/s41413-023-00281-w · Cited by 31 · see citing works
The Role of AOPP in Age-Related Bone Loss and the Potential Benefits of Berry Anthocyanins
Melough, M. M., Sun, X., & Chun, O. K. (2017) · Nutrients · doi:10.3390/nu9070789 · Cited by 29 · see citing works
“It has also been reported that RAGE plays a critical role in osteoclast maturation and activation [39], and RAGE expression in osteoclasts is age-dependent [40].”
BackgroundThe Pathology of Primary Familial Brain Calcification: Implications for Treatment
Xu, X., Sun, H., Luo, J., Cheng, X., Lv, W., Luo, W. F., Chen, W., Xiong, Z., & Liu, J. Y. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00980-0 · Cited by 32 · see citing works
“Furthermore, Aβ enhances the differentiation and activation of osteoclasts [151, 152].”
BackgroundSelf-citationBased on molecular structures: Amyloid-β generation, clearance, toxicity and therapeutic strategies
Yang, H., Li, J., Li, X., Ma, L., Hou, M., Zhou, H., & Zhou, R. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.927530 · Cited by 30 · see citing works
Self-citationFrom the Mind to the Spine: The Intersecting World of Alzheimer’s and Osteoporosis
Margetts, T. J., Wang, H. S., Karnik, S. J., Plotkin, L. I., Movilă, A., Oblak, A. L., Fehrenbacher, J. C., & Kacena, M. A. (2024) · Current Osteoporosis Reports · doi:10.1007/s11914-023-00848-w · Cited by 26 · see citing works
Xie, C.-X., Wang, C.-L., & Luo, H. (2023) · BMC Geriatrics · doi:10.1186/s12877-023-04548-z · Cited by 27 · see citing works
“Aβ is also expressed in nonneural tissues, including osteoblasts and osteoclasts, which can directly impair osteoblast proliferation and increase osteoclast activation [43, 44].”
BackgroundSui, S. X., Balanta‐Melo, J., Pasco, J. A., & Plotkin, L. I. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00736-9 · Cited by 34 · see citing works
Gu, Y., Wu, Z., Zeng, F., Jiang, M., Teeling, J. L., Ni, J., & Takahashi, I. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200689 · Cited by 35 · see citing works
The RAGE signaling in osteoporosis
Zhou, J., Liu, S., Bi, S., Kong, W., Qian, R., Xie, X., Zeng, M., Jiang, X., Liao, Z., Shuai, M., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115044 · Cited by 22 · see citing works
Xiong, L., Xia, W.-F., Tang, F.-L., Pan, J., Mei, L., & Xiong, W. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.05.028 · Cited by 27 · see citing works
“Bonehistomorphometric analyseswere carried out as previously described (Cui et al., 2010; Xia et al., 2013a; Xia et al., 2013b; Zhou et al., 2008; Zhou et al., 2006).”
MethodSelf-citationGuo, J.-P., Pan, J., Xiong, L., Xia, W.-F., Cui, S., & Xiong, W. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139395 · Cited by 24 · see citing works
“The osteoclast (OC) differentiation and activation in Tg2576 mice are also age-dependent and biphasic, with a slight increase of OCs in young adult, but a marked decrease in older age of the mutant mice [7].”
BackgroundMethodInfluentialSelf-citationHepcidin contributes to Swedish mutant APP-induced osteoclastogenesis and trabecular bone loss
Guo, H.-H., Xiong, L., Pan, J., Lee, D., Liu, K., Ren, X., Wang, B., Yang, X., Cui, S., Mei, L., et al. (2021) · Bone Research · doi:10.1038/s41413-021-00146-0 · Cited by 37 · see citing works
Self-citationAGEs and Bone Ageing in Diabetes Mellitus
McCarthy, A. D., Molinuevo, M. S., & Cortizo, A. (2013) · Journal of Diabetes & Metabolism · doi:10.4172/2155-6156.1000276 · Cited by 21 · see citing works
“APPswe has been found to promote osteoclast activation in vivo and in vitro via RAGE, providing a potential mechanism underlying the increased bone fracture rate in patients with Alzheimer’s disease [62].”
BackgroundGlycobiology in osteoclast differentiation and function
Yang, S., He, Z., Wu, T., Wang, S., & Dai, H. (2023) · Bone Research · doi:10.1038/s41413-023-00293-6 · Cited by 21 · see citing works
Alzheimer’s disease and its associated risk of bone fractures: a narrative review
Zhou, B.-N., Zhang, Q., & Li, M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1190762 · Cited by 20 · see citing works
Zhuang, Q.-S., Zheng, H., Gu, X.-D., Shen, L., & Ji, H.-F. (2017) · OncoTarget · doi:10.18632/oncotarget.19115 · Cited by 20 · see citing works
“In addition, increasing evidence support that osteoclast was associated with both obesity and AD [28, 29].”
BackgroundChen, C., Abell, A. M., Moon, Y. S., & Kim, K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.399790 · Cited by 59 · see citing works
Xie, L., Feng, E., Li, S., Chai, H., Chen, J., Li, L., & Ge, J. (2023) · Medicine · doi:10.1097/md.0000000000033829 · Cited by 19 · see citing works
“[20] Additionally, Cui demonstrated a role for APP in regulating osteoclast differentiation in vitro and in vivo.[21] And mutant APP has been shown to suppress OB differentiation and bone formation in culture and in mouse.”
BackgroundStapledon, C. J. M., Stamenkov, R. B., Cappai, R., Clark, J., Bourke, A., Solomon, L. B., & Atkins, G. J. (2021) · Calcified Tissue International · doi:10.1007/s00223-020-00796-y · Cited by 20 · see citing works
Gao, X.-Q., Tang, Y., Amra, S., Sun, X., Cui, Y., Cheng, H.-Z., Wang, B., & Huard, J. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz012 · Cited by 19 · see citing works
Essex, A. L., Huot, J. R., Deosthale, P. J., Wagner, A., Figueras, J. H., Davis, A., Damrath, J. G., Pin, F., Wallace, J. M., Bonetto, A., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4572 · Cited by 21 · see citing works
“Previous work in the amyloid precursor protein (APP) Swedish mutation (APPswe) mouse model of AD has shown bone loss in the distal femur measured by micro-computed tomography (μCT) in young but not in an aged mouse model of plaque neuropathology, as well as increases in osteoclast differentiation of cells from young b…”
BackgroundLuzi, F., Savickas, V., Taddei, C., Hader, S., Singh, N., Gee, A., & Bongarzone, S. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2019-0329 · Cited by 17 · see citing works
Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis
Kumar, S., Song, K., Wang, J., Baghel, M. S., Zeng, Y., Shen, K., Zheng, J., Crane, J., Demehri, S., Gao, P., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00924-z · Cited by 16 · see citing works
Sun, L., Zhang, J.-H., Xiahou, Z.-K., Zhao, Z.-Z., & Liang, Y.-C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1506225 · Cited by 16
Ho, A., Ngala, B., Yamada, C., Garcia, C., Duarte, C. L., Akkaoui, J., Ciolac, D., Nusbaum, A., Kochen, W. R., Efremova, D., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115435 · Cited by 15 · see citing works
Alzheimer’s Disease and Impaired Bone Microarchitecture, Regeneration and Potential Genetic Links
Zhang, M., Hu, S., & Sun, X. (2023) · Life · doi:10.3390/life13020373 · Cited by 14 · see citing works
“APP is a transmembrane protein and, unlike tau proteins, APP is ubiquitously expressed in bone marrow stromal cells (BMSCs), OBs, macrophages (BMMs) and OCs.”
BackgroundInfluentialXia, T.-S., Zhang, J., Guo, Y.-X., Jiang, Y.-P., Qiao, F., Li, K., Wang, N.-N., Han, T., & Xin, H.-L. (2023) · Molecules · doi:10.3390/molecules28020583 · Cited by 15 · see citing works
“SOP may be caused by Aβ deposition in femurs, which affect the activities of osteoblasts and osteoclasts [17].”
BackgroundPan, J., Sun, D., Lee, D., Xiong, L., Ren, X., Guo, H.-H., Yao, L., Lu, Y., Jung, C., & Xiong, W. (2021) · Communications Biology · doi:10.1038/s42003-021-02843-2 · Cited by 16 · see citing works
Self-citationHayman, D. J., Brito, F. M. J. D. S., Lin, H., Prior, A., Charlesworth, G., Hao, Y., Pearson, R. D., Soul, J., Clark, I. M., Piróg, K. A., et al. (2024) · Bone · doi:10.1016/j.bone.2024.117273 · Cited by 13 · see citing works
Bu, X., Liu, Z., Xin, J., Huang, M., Bai, Y., Zhou, J., Bao, Y., Li, J., Liu, Z., Zeng, G., et al. (2025) · MedComm · doi:10.1002/mco2.70255 · Cited by 10 · see citing works
Muscular Swedish mutant APP-to-Brain axis in the development of Alzheimer’s disease
Pan, J., Lee, D., Sun, D., Zhao, K., Xiong, L., Guo, H.-H., Ren, X., Chen, P., de Boer, R. L., Lu, Y., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05378-4 · Cited by 12 · see citing works
Self-citationYang, B., Cai, Z., Zhang, W., Yin, D., Zhao, W., & Yang, M. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.10069 · Cited by 6 · see citing works
“In addition, Aβ has been suggested to enhance the function of osteoclasts (OCs) (10), and gene knockout experiments and the use of Tg2576 mice have identified a role for Aβ in the activation of OCs (29,30), Aβ also enhanced receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand-ind…”
BackgroundJung, Y., Ay, B., Cyr, S. M., Tognoni, C. M., Klovdahl, K., Matthias, J., Cui, Q., Brooks, D. J., Bouxsein, M., Carreras, I., et al. (2024) · Bone Reports · doi:10.1016/j.bonr.2024.101771 · Cited by 10 · see citing works
Suryadevara, V., Klüppel, M., del Monte, F., & Willis, M. S. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.04.013 · Cited by 13 · see citing works
Wang, B., Pan, J., Yu, H., Xiong, L., Zhao, K., Xiong, S., Guo, J.-P., Lin, S., Sun, D., Zhao, L., et al. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3667 · Cited by 13 · see citing works
Self-citationZhang, W., Li, S., Cui, Y., Lun, Y., Liu, H., & Li, M. (2026) · CNS Neuroscience & Therapeutics · doi:10.1002/cns.70754 · Cited by 10 · see citing works
“…differentiation [64]; Notably, these pro-resorptive effects are partially mitigated in aged individuals by upregulation of soluble RAGE (sRAGE) and osteoprotegerin (OPG), though this compensation coincides with impaired bone remodeling and increased fracture susceptibility—hallmarks of aging [72].”
Xu, W., Jiang, Y., Wang, N., Bai, H., Xu, S., Xia, T., & Xin, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.842101 · Cited by 11 · see citing works
“Cui et al. (2011) found that Aβ oligomers and receptors for advanced glycation end products (RAGE) promote OC production in Tg257 mouse models under 4 months of age.”
BackgroundExercise and the Prevention of Osteoporosis
Rubin, C., Rubin, J., & Judex, S. (2013) · Primer on the metabolic bone diseases and disorders of mineral metabolism · doi:10.1002/9781118453926.ch46 · Cited by 10 · see citing works
Karnik, S. J., Margetts, T. J., Wang, H. S., Movilă, A., Oblak, A. L., Fehrenbacher, J. C., Kacena, M. A., & Plotkin, L. I. (2024) · Current Osteoporosis Reports · doi:10.1007/s11914-023-00847-x · Cited by 15 · see citing works
Li, X., Li, X.-Y., Wang, H.-Q., & Zhao, X. (2023) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-023-06664-8 · Cited by 9
Self-citationNi, J., & Wu, Z. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.638686 · Cited by 9 · see citing works
“It is reported that Aβ induces the differentiation and activation of osteoclasts, resulting in the promotion of bone destruction (Cui et al., 2011; Li et al., 2016).”
BackgroundShrestha, P., Basida, B., Elam, R. E., Hajj, J. E., Le, B. K., Fink, H. A., Bethel, M., Tharrington, S. G., & Carbone, L. D. (2025) · Current Osteoporosis Reports · doi:10.1007/s11914-025-00924-3 · Cited by 8 · see citing works
Knockdown of C3aR alleviates age-related bone loss via activation of YAP1/β-catenin signaling
Li, F.-Y., & Cui, S. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108500 · Cited by 5 · see citing works
Self-citationWu, B., Chen, M., Meng, L., Tian, Q., & Dong, Z. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240096 · Cited by 3 · see citing works
Zhang, W.-D., Liu, T., Rong, X., Liu, H.-R., & Li, M.-Q. (2026) · Bone · doi:10.1016/j.bone.2026.117859 · Cited by 2
Šebeková, K., Kovalčíková, A. G., Čagalová, A., Tichá, Ľ., & Podracká, Ľ. (2025) · Archives of Osteoporosis · doi:10.1007/s11657-025-01554-z · Cited by 2 · see citing works
“Moreover, high sRAGE levels have been proposed to inhibit RANKL-induced osteoclastogenesis [49].”
Potential Biological and Genetic Links Between Dementia and Osteoporosis: A Scoping Review
Ogunwale, A., Schulz, P., Bordes, J. K. D., Elefteriou, F., & Rianon, N. (2025) · Geriatrics · doi:10.3390/geriatrics10040096 · Cited by 2
“In line with these results, it is postulated that excess A β exerts its effect on bone in a bone-autonomous manner via osteoclast activation [46].”
Drug discovery in spinal cord injury-induced osteoporosis: a text mining-based study
Wang, C., Xu, Y., Han, L., Wu, W.-Q., & Lu, X.-H. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-6900 · Cited by 2 · see citing works
“APP was reported as a potential biomarker of OP for drug targets (18), and may also be a promising agent for osteoporotic therapy owing to its role in enhancing receptor activator of NF-κ B ligand (RANKL)-induced osteoclast activation (19,20).”
Palermo, A., Naciu, A., Tabacco, G., D'Onofrio, L., & Napoli, N. (2018) · Springer eBooks · doi:10.1007/978-3-319-75110-8_10 · Cited by 2 · see citing works
Xiong, L., Sun, D., Guo, H.-H., Lee, D., Liu, Z.-P., Mei, L., & Xiong, W.-C. (2026) · Advancement of science · doi:10.1002/advs.75622 · Cited by 1
Self-citationSon, H.-J., Park, S.-J., Park, J.-S., & Han, K. (2025) · Osteoporosis International · doi:10.1007/s00198-025-07524-y · Cited by 1 · see citing works
“Pathologically, AD is characterized by the presence of Aβ and neurofibrillary tangles, and Aβ can also be expressed in non-neural tissue, including osteoblasts and osteoclasts, where it can directly impair osteoblast proliferation and increase osteoclast activation [30, 31].”
Saini, D., Khatoon, Z., Bano, U., Mujeeb, M., Ismail, M. V., Akhtar, M., & Najmi, A. K. (2026) · Current Molecular Pharmacology · doi:10.1016/j.cmp.2026.10.001
Wang, J., Cao, X., & Wan, M. (2026) · Journal of Clinical Investigation · doi:10.1172/jci207273
Zheng, J., Gao, Y., Yuan, X., Luo, F., Wang, Z., Song, Z., & Ma, W. (2026) · Food Science & Nutrition · doi:10.1002/fsn3.71931
“Hyperglycemia may promote bone erosion by enhancing osteoclast activity through advanced glycation end products (AGEs) (Cui et al. 2011).”
Tau deficiency contributes to impaired bone formation via activating PPARγ signaling.
Zhu, M., Hu, S., Liu, J., Huang, H., & Sun, X. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.111842
Self-citationAmyloid-β peptide treatment reverses bone loss in the mandibular condyle via Wnt signalling pathway
Chen, Q., Tu, S.-Q., Tang, D.-X., Wei, J., Wei, N., Ai, H., Yang, B., & Chen, Z. (2024) · Bone Reports · doi:10.1016/j.bonr.2024.101788
“However, as soluble RAGE, which inhibits the functions of RAGE, increases in those older transgenic mice ( > 4 months old), it was found that osteoclast activity was suppressed and that bone mass was increased (Cui et al., 2011).”
BackgroundResultNeuropsychiatric Disorders and the Skeleton
Misra, M., & Klibanski, A. (2018) · Wiley eBooks · doi:10.1002/9781119266594.ch134
Neuropsychiatric Disorders and the Skeleton
Bab, I., & Yirmiya, R. (2013) · Wiley eBooks · doi:10.1002/9781118453926.ch120
- Authors
- Cui, S., Xiong, F., Hong, Y., Jung, J.-U., Li, X.-S., Liu, J.-Z., Yan, R., Mei, L., Feng, X., & Xiong, W.-C.
- Affiliations
- Augusta University (US)
- University of Alabama at Birmingham (US)
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
- Cleveland Clinic (US)
- Corresponding author
- Xiong, Wen-Cheng
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-11-23
- Volume
- 26
- Issue
- 5
- Pages
- 1084-1098
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC3126661
- OpenAlex
- W2104811729
- Cited by
- 101
- References
- 49
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 12 · 2023: 15 · 2022: 7 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 7 · 2012: 1
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX000838)
- National Institute on Aging (R01AG051773)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR048120)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- Alzheimer's disease, amyloid precursor protein, APPswe, amyloid-beta, osteoclast activation, osteoclastogenesis, receptor for advanced glycation end products, soluble RAGE, bone remodeling, bone loss, osteoporosis, Tg2576 mice, bone marrow-derived macrophages, RANKL, aging
- MeSH terms
- Receptor for Advanced Glycation End Products, Aging, Animals, Bone and Bones, Bone Marrow Cells, Humans, Injections, Intraperitoneal, Mice, Transgenic, Models, Biological, Mutation, Organ Specificity, Organ Size, Osteoblasts, Osteoclasts, Osteogenesis, Receptors, Immunologic, Solubility, Amyloid beta-Peptides, Protein Structure, Quaternary, Mice, RANK Ligand
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