Effects Of Raloxifene On Lumbar Facet Joint Osteoporotic Osteoarthritis In Ovariectomized Rat Model

Objectives The aim of this research to explore the feasibility for establishing the osteoporotic osteoarthritis(OA)model of facet joint using female Sprague-Dawley(SD)rats induced by bilateral ovariectomy(OVX),and to explore the effects of raloxifene(RAL)on cartilage and subchondral bone of lumbar facet in this model.Methods Thirty 3-month-old SPF grade female SD rats were randomly divided into three groups with 10 rats in each group.Control group(Sham group),modeling group(OVX+V group)and experimental group(OVX+RAL group).Rats in the sham group received sham surgery.Rats in the OVX+V group and OVX+RAL group received bilateral OVX,followed by gavage of normal saline or RAL(10 mg/kg/day)respectively.Twelve weeks after administration,all rats were euthanized,and then lumbar facet joint(L4-L5)was harvested and put into 4% formaldehyde.The lumbar facet joint(L4-L5)was prepared to evaluate subchondral bone histomorphometry by Micro-CT.All the specimens were decalcified for 10 weeks,then embedded,sliced,toluidine blue staining and immunohistochemical staining.The severity of joint lesion was analyzed by Modified Mankin histology score.The expression of Caspase-3 and MMP-13 was detected by IRS score.The experimental data of each group were analyzed by SPSS 20.0 software.Results 1 Micro-CT results showed that bone density,bone volume fraction and trabecular thickness of OVX+V group were significantly lower than those in Sham group,and there were statistical differences between the two groups(P < 0.05).Compared with OVX+V group,the values of BMD,BV/TV and Tb.Th of OVX+RAL group increased,and the difference was statistically significant(P < 0.05).Compared with Sham group,OVX+RAL group had lower bone mineral density(BMD),bone volume/total volume(BV/TV)and trabecular thickness(Tb.Th)values,but only the difference of Tb.Th value was statistically significant(P < 0.05).2 The result of toluidine blue staining analyzed by Modified Mankin histology score in OVX+V group was higher than that in Sham group,and the difference was statistically significant(P < 0.05).The histological score of Modified Mankin in OVX+RAL group was lower than that in OVX+V group,and the difference was statistically significant(P < 0.05).3 The result of mean thickness of cartilage showed,the mean thickness of cartilage in OVX+V group was significantly lower than that in Sham group and the difference was significant(P < 0.05).The mean thickness of cartilage in OVX+RAL group was higher than that in OVX+V group,and the difference was significant(P < 0.05).4 The result of immunohistochemical staining detected by IRS scores of Caspase-3 and MMP-13 protein in OVX+V group were higher than those in Sham group,and the difference was statistically significant(P < 0.05).The scores of Caspase-3 and MMP-13 IRS in OVX+RAL group were significantly lower than those in OVX+V group,and the difference was statistically significant(P < 0.05).Conclusions 1 3-month-old SD female rats can be induced OA like degeneration of the lumbar facet joints at 12 weeks after OVX operation.2 The main pathological changes of osteoporotic OA of lumbar joint after OVX were irregular cartilage surface,small fissure,lower thickness of cartilage,and osteoporosis of subchondral bone.3 Intervent with RAL after OVX,the degree of lumbar articular cartilage lesion improved,the thickness of cartilage increased,and the expression of Caspase-3 and MMP-13 decreased in articular cartilage.Raloxifene is expected to be a potential drug for the treatment of osteoporotic osteoarthritis.