| Objective To observe the effect of strontium ranelate(SR)on the aseptic loosening-induced loosening model in mice around the prosthesis and explore the mechanism of its role in aseptic loosening.Methods This experiment explored the mechanism of SR on total joint replacement.One week after experimental treatment,SR [625 mg/(kg·d)or 1800 mg/(kg·d)] was given orally,and the control group was given the same volume of normal saline.Geriatric female rats were ovariectomized at the same time.After treatment,the animals were sacrificed after 12 weeks of gavage.Micro-CT was used to detect osteolysis around the prosthesis,thickness and quantity of trabecular bone.Immunohistochemical staining was used to observe the expression levels of RANKL and OPG in the joint tissues.RT-PCR was used to measure the expression levels of OPG and RANKL in tissues.IL-1 was measured by ELISA.,TNF-α levels,Western Blot measured RANKL,OPG levels.Results(1)Absorption of bone around the prosthesis of the mouse tibia in the control group can be clearly seen in the horizontal CT scan of the wild-type male C57 total knee replacement model,but after taking the SR drug The degree of bone resorption was significantly reduced in the low-dose group and the high-dose group.In the HE staining results,the results of the control group were compared with those of the low-dose group and the high-dose group.The amount of bone around the prosthesis of the control group was found to be slightly less than that of the other two groups of SR drugs,and the bone mass of the low-dose group was also found.Compared with the high-dose group,the difference in bone mass between the two was small.Similar immunohistochemical staining results showed similar gradient distribution results: in OPG staining,the number of positively stained cells decreased from high dose group to low dose group to control group;RANKL staining increased sequentially.The ELISA results of the inflammatory factors IL-1 and TNF-α showed that in the high-dose SR group,the inflammatory factors in the periprosthetic tissues were the lowest,and the inflammatory factors in the tissues surrounding the prosthesis of the control mice were the most.(2)In the horizontal micro-CT scan of the wild-type female C57 total knee replacement model,bone resorption around the prosthesis of the control group of young and old mice was observed,but in young rats taking SR drugs.The degree of bone resorption was reduced in the experimental group and the aged mice,and the number of trabecular bone and trabecular bone in the drug group of young rats and aged rats was greater than that of the control group.In the HE staining results,the amount of bone around the prosthesis in the two control groups was slightly less than that in the drug group.The amount of bone around the prosthesis of young rats in the drug group was slightly smaller than that of the aged rats,but the difference in bone mass between the two groups was small.In the OPG staining of the same location,the cell positive rate of the young drug group was more than that of the old drug group,and both were higher than the two control groups;in the RANKL staining,the group with the lowest cell positivity rate was the young drug group,followed by the elderly drug In the group,the number of RANKL-positive cells stained most in the two control groups.The ELISA monitoring results of the inflammatory factors IL-1 and TNF-α showed that the inflammatory factors in the two drug groups were lower than those in the control group,and the inflammatory factors in the young drug group were lower than those in the old drug group.(3)Bone mass around the implanted iliac bone of the wild-type and SOST-/-control mice can be seen in the horizontal CT scan of the wild-type and SOST-/-male C57 total knee arthroplasty models.The absorption of the bone around the prosthesis in the wild-type control group was very obvious,while the bone resorption around the prosthesis in the SOST-/-control group was relatively small,and the extent of bone resorption in the two gene expression-type drug groups was significant.The reduction of bone mass around the prosthesis of the SOST-/-drug group was very low,and the number of trabecular bone was also greater than that of the wild-type drug group.The thickness of the trabecular bone was not significantly different between the SOST-/-control group and the wild-type control group.difference.In the HE staining results,the knockout mice had significantly more bone mass than the wild type rats.In the immunohistochemical OPG staining of the same location,the positive rate of the cells in the knockout mice was more than that of the wild type mice,and the positive rate of the cells in the drug group was more than that in the control group;the number of positive cells in the knockout mice was more than that in the RANKL staining.There were fewer wild-type mice,and there were fewer positive staining cells in the drug group than in the control group.Real-time PCR determination of RANKL in the four groups of experimental rats showed that the wild-type control group was the highest,followed by the wild-type drug group,and the control group of the knockout mice again.The RANKL content of the knockout mice experimental group was determined.lowest.The results of OPG assay were contrary to RANKL.The OPG content of both groups was higher than that of wild mice,and the OPG content of the drug group was higher than that of the control group.The results of Western-blot determination of the OPG and RANKL concentrations in the four groups of experimental mice were similar to those obtained by Real-time PCR.The results of RANKL assay were highest in wild-type youth,followed by the wild-type drug group and once again in the knockout mice.In the control group,knockout mice of the drug group had the lowest RANKL content.The results of OPG assay were contrary to RANKL.The OPG content of both groups was higher than that of wild mice,and the OPG content of the drug group was higher than that of the control group.Conclusion The knock-out of SOST gene can deter the effect of SOST on the canonical Wnt pathway and decrease the ratio of RANKL/OPG,which has an inhibitory effect on the peripheral osteolysis of mice induced by abrasive particles.SR has an inhibitory effect on wear debris-induced periprosthetic osteolysis in mice,it can reduce the ratio of RANKL/OPG and prevent the release of inflammatory factors in the absence of SOST. |
