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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1999-8-17
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-10234572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-1724107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-1885867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-2167179,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-3520321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-3789087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-7585968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-7816067,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-8601639,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-8602509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-8968021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9108485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9169344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9182763,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9275093,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9363890,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9464267,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9492069,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9520411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9537505,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9675134,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10430604-9794488
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9738
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
229-37
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10430604-Aging,
pubmed-meshheading:10430604-Animals,
pubmed-meshheading:10430604-Bone Density,
pubmed-meshheading:10430604-Bone Diseases, Metabolic,
pubmed-meshheading:10430604-Bone Marrow Cells,
pubmed-meshheading:10430604-Bone Morphogenetic Proteins,
pubmed-meshheading:10430604-Calcium,
pubmed-meshheading:10430604-Cell Differentiation,
pubmed-meshheading:10430604-Cell Survival,
pubmed-meshheading:10430604-Glucuronidase,
pubmed-meshheading:10430604-Membrane Proteins,
pubmed-meshheading:10430604-Mice,
pubmed-meshheading:10430604-Mice, Transgenic,
pubmed-meshheading:10430604-Osteoblasts,
pubmed-meshheading:10430604-Osteoclasts,
pubmed-meshheading:10430604-Phenotype,
pubmed-meshheading:10430604-RNA, Messenger,
pubmed-meshheading:10430604-Stem Cells
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pubmed:year |
1999
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pubmed:articleTitle |
Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia.
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pubmed:affiliation |
Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan. kawaguchi-ort@h.u-tokyo.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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