Abstract

Senolytic is a potential new anti-aging drug, and it is worth exploring whether it has an inhibitory effect on osteoporosis. Osteoporosis models in mice were established by gavage of retinoic acid(RA), and Senolytic drugs (dasatinib and quercetin) were used to treat for 8w. Serological indexes were measured, and bone mineral density was detected by dual-energy X-ray absorptiometry, then parameters of trabecular bone were quantified by μCT, by which three-dimensional images of lumbar trabecular bone were rebuild for comprehensive analysis. In osteoporosis model mice the content of serum calcium and alkaline phosphatase in mice were increased, the bone mineral density decreased, bone volume fraction and trabecular number decreased significantly, and the trabecular separation increased significantly. After applying the Senolytic drug, the serum calcium of group A and B were significantly lower than that of the blank control group. The alkaline phosphatase content in the two groups was (272.5±42.7)U/L and (258.4±90.2)U/L, which was also significantly lower than that in the blank control group (389.0±31.1)U/L. After the treatment of Senolytic, the bone mineral density of group A and group B were improved, the bone volume fraction were increased compared with the blank control group. The trabecular bone separation of the two groups was significantly reduced. Therefore, these reduced osteoporosis. From our study, it can be confirmed that the senolytic drug has a certain alleviating effect on osteoporosis.

Highlights

  • Experiment materiaExperimental animals: 40 healthy and female SPF KM mice[weighing (30.1±1.6)g] were provided by Hunan Slake Jingda Experimental Animal Co. LTD, production certificate No SCXK(Xiang)2011-0003

  • China has entered an aging society, which has brought a series of problems, among which the great medical challenge is the increasing incidence of diseases related to aging[1]

  • Normal bone is a state of balance between the two, while osteoporosis is caused by the imbalance of bone metabolism and the amount of bone destruction is greater than the amount of bone formation, among which, excessive osteoclast function is the main cause[2]

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Summary

Experiment materia

Experimental animals: 40 healthy and female SPF KM mice[weighing (30.1±1.6)g] were provided by Hunan Slake Jingda Experimental Animal Co. LTD, production certificate No SCXK(Xiang)2011-0003. All mice were raised in the standardized laboratory of Changsha Medical University. The mice were fed in different cages and ate freely. Experimental supplies: Dasatinib and quercetin were donated by Dr Liu Shuiping, School of Life Sciences, Central South University. Phosphorus content, osteocalcin, alkaline phosphatase kit were provided by Nanjing JianCheng Institute of Biological Engineering

Model making and intervention treatment
Detection of bone - related serological indicators
Determination of bone mineral density and bone trabecula
Serological index detection
Bone mineral density
Trabecular bone condition
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