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Loss of cyclin-dependent kinase 1 impairs bone formation, but does not affect the bone-anabolic effects of parathyroid hormone

Takahashi, Akira, (författare)
Tokyo Medical and Dental University
Mulati, Mieradili, (författare)
Tokyo Medical and Dental University
Saito, Masanori, (författare)
Tokyo Medical and Dental University
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Numata, Hoashi, (författare)
Tokyo Medical and Dental University
Kobayashi, Yutaka, (författare)
Tokyo Medical and Dental University
Ochi, Hiroki, (författare)
Tokyo Medical and Dental University
Sato, Shingo, (författare)
Tokyo Medical and Dental University
Kaldis, Philipp, (författare)
National University of Singapore, A*Star Institute of Molecular and Cell Biology (IMCB)
Okawa, Atsushi, (författare)
Tokyo Medical and Dental University
Inose, Hiroyuki, (författare)
Tokyo Medical and Dental University
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Ingår i: Journal of Biological Chemistry. - ASBMB. - 1083-351X. ; 293:50, s. 19387-19399
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
  • Bone mass is maintained by a balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Although recent genetic studies have uncovered various mechanisms that regulate osteoblast differentiation, the molecular basis of osteoblast proliferation remains unclear. Here, using an osteoblast-specific loss-of-function mouse model, we demonstrate that cyclin-dependent kinase 1 (Cdk1) regulates osteoblast proliferation and differentiation. Quantitative RT-PCR analyses revealed that Cdk1 is highly expressed in bone and is down-regulated upon osteoblast differentiation. We also noted that Cdk1 is dispensable for the bone-anabolic effects of parathyroid hormone (PTH). Cdk1 deletion in osteoblasts led to osteoporosis in adult mice due to low bone formation, but did not affect osteoclast formation in vivo Cdk1 overexpression in osteoblasts promoted proliferation, and conversely, Cdk1 knockdown inhibited osteoblast proliferation and promoted differentiation. Of note, we provide direct evidence that PTH's bone-anabolic effects occur without enhancing osteoblast proliferation in vivo Furthermore, we found that Cdk1 expression in osteoblasts is essential for bone fracture repair. These findings may help reduce the risk of nonunion after bone fracture and identify patients at higher risk for nonresponse to PTH treatment. Collectively, our results indicate that Cdk1 is essential for osteoblast proliferation and that it functions as a molecular switch that shifts osteoblast proliferation to maturation. We therefore conclude that Cdk1 plays an important role in bone formation.


MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)


3T3 Cells
Bone and Bones/cytology
CDC2 Protein Kinase/deficiency
Cell Differentiation/drug effects
Cell Proliferation/drug effects
Fractures, Bone/physiopathology
Gene Knockout Techniques
Parathyroid Hormone/pharmacology
Wound Healing/drug effects

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