Retardation in bone resorption after bone marrow ablation in klotho mutant mice

The klotho gene mutant mice exhibit both osteopetrotic phenotype, including elongation of trabeculae in the epiphyses of long bones and vertebral bodies, and osteopenic phenotype, such as thin cortical bones in the diaphyses of these bones. These diverse features raise the question of whether the klotho gene defect results in alteration in bone resorption in vivo. Therefore, we examined the effect of the klotho gene defect on bone resorption by using bone marrow ablation model. At 1 week after bone marrow ablation, trabecular bones were formed in the ablated marrow cavity to levels higher than those in unablated bones in both klotho mutant and wild-type mice. At 2 weeks postsurgery, newly formed trabecular bones were resorbed in wild-type mice to resume normal bone marrow and trabecular bone volume fraction as reported previously. In contrast, the newly formed trabecular bones in the ablated marrow in klotho mutant mice remained at levels similar to those at 1 week. The defect in the bone resorption phase in klotho mutant mice is associated with site-specific reduction of the number and size of osteoclasts in klotho mutant mice. Moreover, the expression levels of osteoprotegerin messenger RNA in the ablated femora of klotho mutant mice were higher than those in wild-type mice. These results indicate that lack of klotho gene expression suppressed bone resorption that should normally take place 2 weeks after bone marrow ablation.