PMID- 10430604
OWN - NLM
STAT- MEDLINE
DCOM- 19990817
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 3
DP  - 1999 Aug
TI  - Independent impairment of osteoblast and osteoclast differentiation in klotho
      mouse exhibiting low-turnover osteopenia.
PG  - 229-37
AB  - 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.
FAU - Kawaguchi, H
AU  - Kawaguchi H
AD  - Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo,
      Tokyo 113-8655, Japan. kawaguchi-ort@h.u-tokyo.edu
FAU - Manabe, N
AU  - Manabe N
FAU - Miyaura, C
AU  - Miyaura C
FAU - Chikuda, H
AU  - Chikuda H
FAU - Nakamura, K
AU  - Nakamura K
FAU - Kuro-o, M
AU  - Kuro-o M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - EC 3.2.1.31 (klotho protein)
RN  - SY7Q814VUP (Calcium)
SB  - AIM
SB  - IM
MH  - Aging/genetics
MH  - Animals
MH  - Bone Density/genetics
MH  - Bone Diseases, Metabolic/diagnostic imaging/*genetics/*pathology/physiopathology
MH  - Bone Marrow Cells/pathology
MH  - Bone Morphogenetic Proteins/biosynthesis/genetics/physiology
MH  - Calcium/blood/urine
MH  - Cell Differentiation/genetics
MH  - Cell Survival/genetics
MH  - Glucuronidase
MH  - Membrane Proteins/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Osteoblasts/*pathology
MH  - Osteoclasts/*pathology
MH  - Phenotype
MH  - RNA, Messenger/biosynthesis
MH  - Radiography
MH  - Stem Cells/pathology
PMC - PMC408412
EDAT- 1999/08/03 00:00
MHDA- 1999/08/03 00:01
CRDT- 1999/08/03 00:00
PHST- 1999/08/03 00:00 [pubmed]
PHST- 1999/08/03 00:01 [medline]
PHST- 1999/08/03 00:00 [entrez]
AID - 10.1172/JCI5705 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Aug;104(3):229-37. doi: 10.1172/JCI5705.