RGD Reference Report - APPswe/Abeta regulation of osteoclast activation and RAGE expression in an age-dependent manner. - Rat Genome Database

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APPswe/Abeta regulation of osteoclast activation and RAGE expression in an age-dependent manner.

Authors: Cui, S  Xiong, F  Hong, Y  Jung, JU  Li, XS  Liu, JZ  Yan, R  Mei, L  Feng, X  Xiong, WC 
Citation: Cui S, etal., J Bone Miner Res. 2011 May;26(5):1084-98. doi: 10.1002/jbmr.299.
RGD ID: 6767561
Pubmed: PMID:21542009   (View Abstract at PubMed)
PMCID: PMC3126661   (View Article at PubMed Central)
DOI: DOI:10.1002/jbmr.299   (Journal Full-text)

Alzheimer's disease (AD), one of the most dreaded neurodegenerative disorders, is characterized by cortical and cerebrovascular amyloid beta peptide (Abeta) 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 Abeta 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, 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 Abeta 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/Abeta, reveal a mechanism underlying altered bone remodeling in AD patients, and implicate APP/Abeta and RAGE as common denominators for both AD and osteoporosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
osteoporosis  ISOAger (Mus musculus)6767561; 6767561 RGD 
osteoporosis  IEP 6767561 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Mus musculus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Homo sapiens)
AGER  (advanced glycosylation end-product specific receptor)


Additional Information