2022, Vol. 26 ›› Issue (20): 3152-3157

Abnormally expressed beta-amyloid affects bone metabolism

Li Fangyu, Xia Wenfang, Cui Shun   

Abstract: BACKGROUND: Amyloid β exists widely in human tissues, and its abnormal expression is closely related to various chronic inflammatory diseases such as Alzheimer’s disease and osteoporosis. Studies have shown that amyloid β deposits in human vertebrae and femur and then causes bone destruction. However, the effect of low expression of amyloid β on bone metabolism remains unclear.  
OBJECTIVE: To investigate the effect of overexpression and low expression of amyloid β on bone metabolism in mice.
METHODS: There were three groups: an APPswe+/+ group with APPswe+/+ transgenic mice aged 12 months with overexpression of amyloid β, a BACE-/- group with β-secretase cleaving enzyme-1 gene knockout mice with low expression of amyloid β, and a wild type group with wild type mice. Amyloid β deposition in bone tissue was observed by Congo red staining. Immunohistochemical staining was used to detect the distribution of amyloid precursor protein in bone tissue, and micro-computed tomography was used to study the difference of overall bone structure. Alkaline phosphatase staining and tartrate-resistant acid phosphatase staining were used to analyze the differences between bone formation and bone resorption.  
RESULTS AND CONCLUSION: Compared with the wild type group, amyloid β deposition of cancellous bone and compact bone was increased in the APPswe+/+ group, and decreased in the BACE-/- group (P < 0.05). Compared with the wild type group, the expression of amyloid precursor protein in mouse cancellous bone was increased in the APPswe+/+ and BACE-/- groups. Compared with the wild type group, the bone mass and thickness of trabecular bone were decreased, and trabecular bone became thinner, sparse, disordered or fractured in the APPswe+/+ and BACE-/- groups. There was also abnormal bone formation and enhanced activity of osteoclasts in the APPswe+/+ and BACE-/- groups   (P < 0.05). To conclude, overexpression or low expression of amyloid β can cause bone metabolism disorder and lead to bone loss. Abnormal lower expression of amyloid β caused by β-secretase cleaving enzyme-1 gene knockout can affect the expression of amyloid precursor protein in bone, and lead to an abnormal bone metabolism.
Key words: amyloid β, bone metabolism, β-secretase cleaving enzyme-1, amyloid precursor protein, bone destruction