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 functi on of bone forming osteoblasts, we have examined the steady-state mRNA leve ls of the transcription factor CBFA1 and topoisomerase I during cellular ag ing of normal human trabecular osteoblasts, by the use of semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). There is a progre ssive and significant reduction of the CBFA1 steady-state mRNA level down t o 50% during cellular aging of human osteoblasts. In comparison to the norm al tells, human osteosarcoma cell lines SaOS-2 and KHOS/NP, and the SV40-tr ansformed human lung fibroblast cell line MRC5V2 have 20 to 40% higher leve ls of CBFA1 mRNA. Similar levels of CBFA1 mRNA are detectable in normal hum an 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 hig her (40-70%) in transformed osteoblasts and fibroblasts. These changes in g ene expression may he among the causes of impaired osteoblast functions, re sulting in reduced bone formation during aging.