Abstract: Abstract: Objective To research on the effect of the recombinant adeno-associated virus vector containing klotho gene delivery to regulate for ovariectomized rats.Methods Female SD rats were randomly divided into sham operation group (S group) and model group.Model was successfully constructed with ovariectomy after 12 weeks,they were randomly divided into model group (O group), 17β-estradiol (E group), klotho gene group (KO group), empty vector group (GO group), all were sacrificed after 12 weeks.Bone mineral density(BMD) of the femurs and tibia were measured. The fluorescent expression of renal klotho was observed by Cryo-sectioning Technique.The Runx2 and MMP-13 mRNA expression of bone tissue were detected by reverse transcription-polymerase chain reaction(RT-PCR).Expression of klotho protein in kidney and Runx2,MMP-13 protein in bone were detected by immunohistochemistry. Bone morphological changes of the different groups were observed by HE staining.Results BMD of KO and E groups were significantly higher than those in the O and GO groups(P<0.05). Specific expression of mouse klotho was seen only in KO group.Renal klotho protein in KO group were increased obviously by immunohistochemistry.Compared to O group,the expression of Runx2 mRNA increased greatly,but the expression of MMP-13 mRNA decreased in bone tissue of KO group (P<0.05). Immunohistochemistry analysis showed,the average absorbance of Runx2 was 411±96 in KO group,it was a significant higher than 353±50 of O group(P<0.05). The average absorbance of MMP-13 was 397±84 in KO group,the value of O group was 656±89,so KO group showed a significantly lower than those in O group (P<0.05).The trabecular bones in KO,E,S groups tightly packed, interconnected to form a network,had relatively complete histologic structure.Conclusion Klotho gene delivery attenuates the progression of osteoporosis and bone microstructure damage in ovariectomized rats, these results suggest that klotho gene may play a role in the progression of osteoporosis.

Key words: Key words: osteoporosis, klotho, Runx2, MMP-13, bone metabolism