Effects of C3aR and receptor for advanced glycation end products on bone metabolism in APP/PS1 mice models of Alzheimer′s disease / 中华内分泌代谢杂志

ABSTRACT

Objective:To investigate the effects of complement C3a receptor(C3aR) and receptor for advanced glycation end product(RAGE) on bone metabolism in APP/PS1 mice model of Alzheimer′s disease.Methods:Alzheimer′s disease model APP/PS1 mice was hybridized with C3aR knockout mice(C3aR -/-), RAGE knockout mice(RAGE -/-) to generate APP/PS1-C3aR -/- and APP/PS1-RAGE -/-, respectively. In vivo, micro computed tomography(Micro-CT) scan, bone tissue osteocalcin immunohistochemical staining, tartrate-resistant acid phosphatase(TRAP) staining and Goldner′s trichrome staining were used to understand the variabilities of bone metabolism between different genotypes of mice; In vitro, bone marrow-derived osteoblast and osteoclast induction cultures were used to understand the effects of C3aR and RAGE on osteoblast and osteoclast differentiation. Results:In in vivo experiments, APP/PS1-C3aR -/- and APP/PS1-RAGE -/- mice showed increased bone mass, increased bone formation, decreased bone resorption, and increased osteoid compared to APP/PS1 mice( P<0.05). In in vitro experiments, bone marrow mesenchymal stem cells(BMSCs) derived from APP/PS1-C3aR -/- and APP/PS1-RAGE -/- mice showed enhanced osteoblast differentiation and elevated expression levels of alkaline phosphatase(ALP) and runt-related transcription factor 2(RUNX2), diminished osteoclast differentiation, and reduced positive TRAP staining( P<0.05). Conclusions:Both C3aR and RAGE are involved in regulating the process of APP/PS1 bone metabolism. Knockout of C3aR and RAGE can improve osteoporosis in APP/PS1, providing a new target for the clinical treatment of Alzheimer′s disease combined with osteoporosis.