Effect Of Strontium Ranelate On Articular Cartilage And Subchondral Bone In Guinea Pigs With Secondary Osteoarthritis Model

Objectives The purpose of this study is to explore the protective effect, especially of articular cartilage and subchondral bone, that early intervention of Strontium Ranelate(SR) in a secondary osteoarthritis model of Dunkin-Hartley guinea pigs(DH guinea pig), which induced by medial meniscectomy(MMT).Methods Thirty-six SPF grade three-month-old DH guinea pigs, than were randomly divided into three groups with 12 animals each, namely: Sham group, MMT+NS group and MMT+SR group. MMT were performed on right knees of animals in MMT+NS group and MMT+SR group, and Sham group were operated that only incision to subcutaneous tissue followed by suturing skin. After a week,SR were administrated on MMT+SR group in a dose of 625mg/kg·d by gavage, and the same volume of saline were given to MMT+NS group, and Sham group left no treatment. All animals were sacrificed at the end point of 12 week of administration, then right knee were harvested. Half of the specimen were examined cartilage appearance and synovium, and evaluate OARSI marcoscopic score. The knee tibial bone were send to evaluate bone density and histomorphometry by MicroCT. The other half of the specimen were following decalcified, paraffin-embedded, and sectioned. The sections were stained by toluidine blue or performed immunohistochemistry by incubating with primary anti-body of Col-II, MMP-3, OPG, and RANKL, respectively. Toluidine blue stained sections were assessed in accordance with OARSI histological score. The expression level of specific proteins in IHC stained sections were evaluated by immunoradioactive score, and expression differenance of positive chondrocytes in articular cartilage for each group of DH guinea pigs were analyzed statistically. Ipsilateral specimens of MMT+NS group were compared with Sham group to verify the modeling success, were compared with MMT+SR group to observe the protective effect of SR on OA cartilage and subchondral bone.Results The OARSI scores,Tb.Sp and MMP-3 expression level was significantly higher than in Sham group(P<0.05) than MMT+NS group, BMD, BV/TV,Tb.Th and Col-II expression, were significantly lower than the Sham group(P<0.05), OPG/RANKL and Tb.N showed no significantly difference. BMD, BV/TV and Tb.Th were significantly higher in MMT+SR group than MMT+NS group(P<0.05), Tb.Sp were significantly lower than the MMT+NS group(P<0.05),however, OARSI histological scores, the expression level of other factors and Tb.N showed no significant difference between MMT+SR group and MMT+NS group.Conclusions 1 articular cartilage and subchondral bone of DH guinea after MMT exhibits similar changes to human OA secondary pathological changes, and therefore is a reliable animal model for studying the pathogenesis of OA. 2 Treatment with SR 625 mg/kg?d for 12 weeks significantly reduced subchondral bone loss on secondary OA model of DH guinea pigs, however, but it did not show a significant effect on cartilage degeneration.