| Objective To investigate the effect of aspirin (ASP) combined with strontium ranelate (SR) on osteoblasts and bone mineral density and bone mass in ovariectomized rats, and to explore the possible mechanism. Methods Firstly, the effect of ASP, SR and SR+ASP on ALP staining and Alizarin red staining of MC3T3-E1 cells were observed. Then the model of postmenopausal osteoporosis was established using bilateral ovariectomy. The ovariectomized rats were randomly divided into OVX group, ASP group, SR group, and SR+ASP group. The rats in ASP group, SR group and SR+ASP group received aspirin, strontium ranelate, or the combination, respectively, for 12 weeks. After the treatment, micro-CT, HE staining, and Western blotting were used to observe the therapeutic effect and possible mechanism. Results Osteoblast experiment showed that ASP, SR, and SR+ASP promoted ALP production and mineralization of osteoblasts. SR+ASP had the most significant effect on ALP production and mineralization of osteoblasts. After 12 weeks of treatment, compared with those in ASP group and SR group, the number of bone trabeculae and bone mineral density in SR+ASP group significantly improved. The levels of BMD, TV/BV, Tb.N, Tb.Th, and Tb.Sp in SR+ASP group were significantly better than those in SR group and ASP group. Compared with that in ASP group and SR group, Notch signal pathway was activated and the levels of Notch-1, CBF-1, and Jagged-1 were significantly up-regulated in SR+ASP group. Conclusion ASP combined with SR can improve the function of osteoblasts and protect bone mass in ovariectomized rats. This effect may be mediated by Notch signal pathway. |