Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia

Hiroshi Kawaguchi, Noriyo Manabe, Chisato Miyaura, Hirotaka Chikuda, Kozo Nakamura, Makoto Kuro-o

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Abstract

We recently identified a new gene, klotho, which is involved in the suppression of multiple aging phenotypes. The mouse homozygous for a disruption of the klotho locus (kl/kl) exhibited multiple pathological conditions resembling human aging. Histomorphometric analysis revealed low- turnover osteopenia in kl/kl mice. The decrease in bone formation exceeded that of bone resorption, resulting in a net bone loss. The number of osteoblast progenitors determined by ex vivo bone marrow cultures was reduced in kl/kl mice. In addition, cultured osteoblastic cells derived from kl/kl mice showed lower alkaline phosphatase activity and matrix nodule formation than those from wild-type mice. Osteoclastogenesis in the coculture of marrow cells and osteoblastic cells was decreased only when marrow cells originated from kl/kl mice independently of the origin of osteoblastic cells. We also found that the expression of osteoprotegerin, an osteoclastogenesis inhibitor, was significantly upregulated in kl/kl mice. We conclude that a defect in the klotho gene expression causes the independent impairment of both osteoblast and osteoclast differentiation, leading to low-turnover osteopenia. Because this state represents a characteristic feature of senile osteoporosis in humans, kl/kl mice can be regarded as a useful model for investigating cellular and molecular mechanisms of age-related bone loss.

Original languageEnglish (US)
Pages (from-to)229-237
Number of pages9
JournalJournal of Clinical Investigation
Volume104
Issue number3
StatePublished - Aug 1999

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Metabolic Bone Diseases
Osteoclasts
Osteoblasts
Osteogenesis
Bone Marrow
Osteoporosis
Osteoprotegerin
Bone Resorption
Coculture Techniques
Alkaline Phosphatase
Cultured Cells
Phenotype
Gene Expression
Bone and Bones

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kawaguchi, H., Manabe, N., Miyaura, C., Chikuda, H., Nakamura, K., & Kuro-o, M. (1999). Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. Journal of Clinical Investigation, 104(3), 229-237.

Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. / Kawaguchi, Hiroshi; Manabe, Noriyo; Miyaura, Chisato; Chikuda, Hirotaka; Nakamura, Kozo; Kuro-o, Makoto.

In: Journal of Clinical Investigation, Vol. 104, No. 3, 08.1999, p. 229-237.

Research output: Contribution to journalArticle

Kawaguchi, H, Manabe, N, Miyaura, C, Chikuda, H, Nakamura, K & Kuro-o, M 1999, 'Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia', Journal of Clinical Investigation, vol. 104, no. 3, pp. 229-237.
Kawaguchi, Hiroshi ; Manabe, Noriyo ; Miyaura, Chisato ; Chikuda, Hirotaka ; Nakamura, Kozo ; Kuro-o, Makoto. / Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 3. pp. 229-237.
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