CBFA1 and topoisomerase I mRNA levels decline during cellular aging of human trabecular osteoblasts.
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.
Christiansen
M
M
Danish Centre for Molecular Gerontology, Department of Molecular and Structural Biology, University of Aarhus, Denmark.
Kveiborg
M
M
Kassem
M
M
Clark
B F
BF
Rattan
S I
SI
D000328:Adult; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence; D050659:Core Binding Factor Alpha 1 Subunit; D004264:DNA Topoisomerases, Type I / Q000032:analysis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000032:analysis; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D004264:DNA Topoisomerases, Type I