Mutation in aging suppressor gene, Klotho, causes decreases in bone formation and resorption in mice

H. Kawaguchi, K. Nakamura, N. Ogata, N. Manabe, H. Chikuda, K. I. Kawano, M. Kuro-O

Research output: Contribution to journalArticle

Abstract

The mouse homozygous for a disruption of the klotho locus (KL-(/)- or klotho mouse) exhibited multiple pathological conditions resembling human ageing. 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 the net bone loss. This pathophysiology shows close resemblance to 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 (TRAP)-positive multinucleated osteoclastic cells was extremely poor only when osteoclast precursor cells originated from KL-(/)- mice independently of the origin of 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.

Original languageEnglish (US)
Pages (from-to)295-301
Number of pages7
JournalConnective Tissue
Volume32
Issue number3
StatePublished - 2000

Fingerprint

Suppressor Genes
Bone Resorption
Osteogenesis
Mutation
Osteoclasts
Osteoporosis
Osteoprotegerin
Bone Remodeling
Metabolic Bone Diseases
Coculture Techniques
Osteoblasts
Alkaline Phosphatase
Cell Differentiation
Cultured Cells
Gene Expression
Bone and Bones

Keywords

  • Aging
  • Bone formation
  • Bone resorption
  • Mutation

ASJC Scopus subject areas

  • Rheumatology

Cite this

Kawaguchi, H., Nakamura, K., Ogata, N., Manabe, N., Chikuda, H., Kawano, K. I., & Kuro-O, M. (2000). Mutation in aging suppressor gene, Klotho, causes decreases in bone formation and resorption in mice. Connective Tissue, 32(3), 295-301.

Mutation in aging suppressor gene, Klotho, causes decreases in bone formation and resorption in mice. / Kawaguchi, H.; Nakamura, K.; Ogata, N.; Manabe, N.; Chikuda, H.; Kawano, K. I.; Kuro-O, M.

In: Connective Tissue, Vol. 32, No. 3, 2000, p. 295-301.

Research output: Contribution to journalArticle

Kawaguchi, H, Nakamura, K, Ogata, N, Manabe, N, Chikuda, H, Kawano, KI & Kuro-O, M 2000, 'Mutation in aging suppressor gene, Klotho, causes decreases in bone formation and resorption in mice', Connective Tissue, vol. 32, no. 3, pp. 295-301.
Kawaguchi H, Nakamura K, Ogata N, Manabe N, Chikuda H, Kawano KI et al. Mutation in aging suppressor gene, Klotho, causes decreases in bone formation and resorption in mice. Connective Tissue. 2000;32(3):295-301.
Kawaguchi, H. ; Nakamura, K. ; Ogata, N. ; Manabe, N. ; Chikuda, H. ; Kawano, K. I. ; Kuro-O, M. / Mutation in aging suppressor gene, Klotho, causes decreases in bone formation and resorption in mice. In: Connective Tissue. 2000 ; Vol. 32, No. 3. pp. 295-301.
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