caa a22 4500 475846249 CHVBK 20180406123915.0 cr unu---uuuuu 170329e20000501xx s 000 0 eng 10.1007/s000180050037 doi (NATIONALLICENCE)springer-10.1007/s000180050037 Cellular and molecular mechanism of low-turnover osteopenia in the klotho-deficient mouse [Elektronische Daten] [H. Kawaguchi*, N. Manabe, H. Chikuda, K. Nakamura, M. Kuro-o] Abstract.: The mouse homozygous for a disruption of the klotho locus (KL −/− or klotho mouse) exhibited multiple pathological conditions resembling human aging. We observed osteopenia in KL −/− mice with a low bone turnover, in which the decrease in bone formation exceeded the decrease in bone resorption and resulted in net bone loss. This pathophysiology resembles closely that of senile osteoporosis in humans. Osteoblastic cells from KL −/− mice proliferated normally in vitro; however, they showed much lower alkaline phosphatase activity and mineralized matrix formation than those from control mice. Cultured osteoclastic cells from KL −/− mice had normal resorbing activity and survival rate, but the differentiation of osteoclastic cells from their precursors was significantly disturbed: in the co-culture of osteoblastic cells and osteoclast precursor cells, the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclastic cells was extremely poor only when osteoclast precursor cells orginated from KL −/− mice independently of the origin of the osteoblastic cells. In addition, we found that osteoprotegerin a secreted factor which inhibits osteoclastogenesis, was up-regulated in KL −/− mice. We conclude that a defect in klotho gene expression leads to the independent impairment of osteoblast and osteoclast differentiation, which can be a cause of low-turnover osteoporosis. Birkhäuser Verlag Basel,, 2000 Key words. Aging nationallicence osteoporosis nationallicence osteoprotegerin nationallicence klotho nationallicence bone nationallicence Kawaguchi* H. Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 (Japan), Fax + 81 33818 4082, e-mail: kawaguchi-ort@h.u-tokyo.ac. jp, JP aut Manabe N. Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 (Japan), Fax + 81 33818 4082, e-mail: kawaguchi-ort@h.u-tokyo.ac. jp, JP aut Chikuda H. Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 (Japan), Fax + 81 33818 4082, e-mail: kawaguchi-ort@h.u-tokyo.ac. jp, JP aut Nakamura K. Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 (Japan), Fax + 81 33818 4082, e-mail: kawaguchi-ort@h.u-tokyo.ac. jp, JP aut Kuro-o M. Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, (Texas 75235-9072, USA), US aut https://doi.org/10.1007/s000180050037 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s000180050037 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kawaguchi* H. Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 (Japan), Fax + 81 33818 4082, e-mail: kawaguchi-ort@h.u-tokyo.ac. jp, JP aut NATIONALLICENCE 700 1- Manabe N. Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 (Japan), Fax + 81 33818 4082, e-mail: kawaguchi-ort@h.u-tokyo.ac. jp, JP aut NATIONALLICENCE 700 1- Chikuda H. Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 (Japan), Fax + 81 33818 4082, e-mail: kawaguchi-ort@h.u-tokyo.ac. jp, JP aut NATIONALLICENCE 700 1- Nakamura K. Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 (Japan), Fax + 81 33818 4082, e-mail: kawaguchi-ort@h.u-tokyo.ac. jp, JP aut NATIONALLICENCE 700 1- Kuro-o M. Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, (Texas 75235-9072, USA), US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer