Strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates ameliorate bone loss in ovariectomized mice / 中国组织工程研究

ABSTRACT

BACKGROUND:Inhibition of osteoclast activity by bisphosphonates slows the progression of osteoporosis.However,serious complications of bisphosphonates,such as osteonecrosis of the jaw and atypical femur fracture,limit the clinical application of bisphosphonates.Effective alternative therapies need to be sought to improve existing clinical dilemmas. OBJECTIVE:To prepare strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates(BPS@Sr-MBG)and analyze its activity against bone loss. METHODS:Strontium-containing mesoporous bioactive glass nanoparticles(Sr-MBG)were prepared by sol-gel method and added to alendronate saturated solution for the preparation of BPS@Sr-MBG.(1)Cell experimentMouse bone marrow macrophages were inoculated in 96-well plates and supplemented with ɑ-MEM complete culture medium containing macrophage colony stimulating factor and activator-ligand of nuclear factor κB receptor for osteoclast induced differentiation experiment.Meanwhile,they were cultured in three groups.The blank group was added with PBS.The control group was added with bisphosphonate,and the experimental group was added with BPS@Sr-MBG.After 5 days of culture,the differentiation of osteoclasts was observed by F-actin ring staining.(2)Animal experimentsTwenty-four female C57/BL mice were randomly divided into four groups with six mice in each group.Except sham operation group,ovariectomy group,BPS group and BPS@Sr-MBG group were used to construct osteoporosis model.One week after model establishment,mice in BPS group and BPS@Sr-MBG group were intraperitoneally injected with bisphosphonate solution and BPS@Sr-MBG solution,respectively.Mice in the sham operation group and ovariectomy group were intraperitoneally injected with PBS once a week.After 8 weeks of continuous injection,mouse femurs were taken for Micro-CT scanning and hematoxylin-eosin staining. RESULTS AND CONCLUSION:(1)Cell experimentF-actin ring-formation staining demonstrated that compared with blank group,the area proportion and number of osteoclasts in the control group were decreased(P<0.01).Compared with the control group,the area proportion of osteoclasts and the number of osteoclasts in the experimental group were decreased(P<0.01).(2)Animal experimentsMicro-CT scanning results of femur showed that compared with the sham operation group,bone density,trabecular bone volume fraction,trabecular thickness and trabecular number of mice in the ovariectomy group were decreased(P<0.05,P<0.01),while trabecular distance and structural model index were increased(P<0.01).Compared with the ovariectomy group,the above bone parameters in the BPS group and BPS@Sr-MBG group were significantly improved(P<0.01),and the improvement in the BPS@Sr-MBG group was more obvious.The Micro-CT scanning results were further confirmed by hematoxylin-eosin staining of the femur.(3)The results show that BPS@Sr-MBG can exert anti-osteoporosis activity through anti-osteoclastic effect and promoting bone formation.