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CBFA1 and Topoisomerase I mRNA Levels Decline During Cellular Aging of Human Trabecular Osteoblasts

^a Danish Centre for Molecular Gerontology, Laboratory of Cellular Ageing, Department of Molecular and Structural Biology
^b University Department of Endocrinology and Metabolism, University of Aarhus, Denmark.

Suresh I. S. Rattan, Laboratory of Cellular Ageing, Department of Molecular and Structural Biology, University of Aarhus, Gustav Wiedsvej 10 C, DK-8000 Aarhus C, Denmark E-mail: rattan{at}imsb.au.dk.

Decision Editor: Jay Roberts, PhD

In order to understand the reasons for age-related impairment of the function of bone forming osteoblasts, we have examined the steady-state mRNA levels of the transcription factor CBFA1 and topoisomerase I during cellular aging of normal human trabecular osteoblasts, by the use of semiquantitative reverse transcriptase–polymerase chain reaction (RT-PCR). There is a progressive and significant reduction of the CBFA1 steady-state mRNA level down to 50% during cellular aging of human osteoblasts. In comparison to the normal cells, human osteosarcoma cell lines SaOS-2 and KHOS/NP, and the SV40-transformed human lung fibroblast cell line MRC5V2 have 20 to 40% higher levels of CBFA1 mRNA. Similar levels of CBFA1 mRNA are detectable in normal human skin fibroblasts, and these cells also exhibit an age-related decline to the same extent. In addition, the expression of topoisomerase I is reduced by 40% in senescent osteoblasts, and the mRNA levels are significantly higher (40–70%) in transformed osteoblasts and fibroblasts. These changes in gene expression may be among the causes of impaired osteoblast functions, resulting in reduced bone formation during aging.

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