This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yamashita, T. Articles by Noda, M. Search for Related Content PubMed PubMed Citation Articles by Yamashita, T. Articles by Noda, M.

Retardation in Bone Resorption after Bone Marrow Ablation in Klotho Mutant Mice¹

Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (T.Y., H.Y., K.T., N.K., M.N.), Tokyo 101-0062; the Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University (Y.-i.N.), Kyoto 606-8501; and the Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan

Address all correspondence and requests for reprints to: Dr. Masaki Noda, Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 3–10, Kanda-Surugadai 2-Chome, Chiyoda-ku, Tokyo, 101-0062, Japan. E-mail: noda.mph{at}mri.tmd.ac.jp

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.

This article has been cited by other articles:

				T. Yamashita, S. Okada, K. Higashio, Y.-i. Nabeshima, and M. Noda Double Mutations in Klotho and Osteoprotegerin Gene Loci Rescued Osteopetrotic Phenotype Endocrinology, December 1, 2002; 143(12): 4711 - 4717. [Abstract] [Full Text] [PDF]