Retardation in bone resorption after bone marrow ablation in klotho mutantmice

The klotho gene mutant mice exhibit both osteopetrotic phenotype, including elongation of trabeculae in the epiphyses of long bones and vertebral bodi es, and osteopenic phenotype, such as thin cortical bones in the diaphyses of these bones. These diverse features raise the question of whether the kl otho gene defect results in alteration in bone resorption in vivo. Therefor e, we examined the effect of the klotho gene defect on bone resorption by u sing bone marrow ablation model. At 1 week after bone marrow ablation, trab ecular 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 we eks postsurgery, newly formed trabecular bones were resorbed in wild-type m ice to resume normal bone marrow and trabecular bone volume fraction as rep orted previously. In contrast, the newly formed trabecular bones in the abl ated 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 asso ciated with site-specific reduction of the number and size of osteoclasts i n klotho mutant mice. Moreover, the expression levels of osteoprotegerin me ssenger RNA in the ablated femora of klotho mutant mice were higher than th ose in wild-type mice. These results indicate that lack of klotho gene expr ession suppressed bone resorption that should normally take place 2 weeks a fter bone marrow ablation.