Effects of telomerase and viral oncogene expression on the in vitro growth of human chondrocytes.
Senescent chondrocytes accumulate with aging in articular cartilage, a process that interferes with cartilage homeostasis and increases the risk of cartilage degeneration. We showed previously that chondrocyte telomere length declines with donor age, which suggests that the aging process is telomere dependent. From these results we hypothesized that telomerase should delay the onset of senescence in cultured chondrocytes. Population doubling limits (PDL) were determined for chondrocytes expressing telomerase. We found that telomerase alone did not extend PDL beyond controls that senesced after 25 population doublings. The human papillomavirus 16 oncogenes E6 and E7 were transduced into the same cell population to investigate this telomere-independent form of senescence further. Chondrocytes expressing E6 and E7 grew longer than the telomerase cDNA (hTERT) cells but still senesced at 55 population doublings. In contrast, chondrocytes expressing telomerase with E6 and E7 grew vigorously past 100 population doublings. We conclude that although telomerase is necessary for the indefinite extension of chondrocyte life span, telomere-independent senescence limits PDL in vitro and may play a role in the age-related accumulation of senescent chondrocytes in vivo.
Martin
James A
JA
Department of Orthopaedic Surgery, The University of Iowa, Iowa City 52242, USA. james-martin@uiowa.edu
Mitchell
Calista J
CJ
Klingelhutz
Aloysius J
AJ
Buckwalter
Joseph A
JA
D002478:Cells, Cultured; D019902:Chondrocytes / Q000201:enzymology* / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009857:Oncogenes / Q000502:physiology*; D027383:Papillomaviridae / Q000235:genetics; D019098:Telomerase / Q000502:physiology*
D019098:Telomerase