Cellular and molecular mechanism of low-turnover osteopenia in the klotho-deficient mouse

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 originated 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.

Original languageEnglish (US)
Pages (from-to)731-737
Number of pages7
JournalCellular and Molecular Life Sciences
Volume57
Issue number5
DOIs
StatePublished - 2000

Fingerprint

Metabolic Bone Diseases
Bone
Osteoclasts
Osteoprotegerin
Osteoblasts
Acid Phosphatase
Osteogenesis
Gene expression
Osteoporosis
Alkaline Phosphatase
Aging of materials
Cells
Defects
Bone Remodeling
Bone Resorption
Coculture Techniques
Cell Differentiation
Cultured Cells
Gene Expression
Bone and Bones

Keywords

  • Aging
  • Bone
  • Klotho
  • Osteoporosis
  • Osteoprotegerin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Cellular and molecular mechanism of low-turnover osteopenia in the klotho-deficient mouse. / Kawaguchi, H.; Manabe, N.; Chikuda, H.; Nakamura, K.; Kuro-O, M.

In: Cellular and Molecular Life Sciences, Vol. 57, No. 5, 2000, p. 731-737.

Research output: Contribution to journalArticle

Kawaguchi, H. ; Manabe, N. ; Chikuda, H. ; Nakamura, K. ; Kuro-O, M. / Cellular and molecular mechanism of low-turnover osteopenia in the klotho-deficient mouse. In: Cellular and Molecular Life Sciences. 2000 ; Vol. 57, No. 5. pp. 731-737.
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