Adenoviral vector expressing IGF-1 protects murine chondrogenic ATDC5 cells against hydrogen peroxide-induced mitochondrial dysfunction and apoptosis.
Insulin-like growth factor-1 (IGF-1), with an age-related decline, regulates the proliferation and survival of multiple cell types, particularly stimulates cartilage matrix synthesis, and inhibits matrix degradation. The present study was to investigate the regulatory role of IGF-1 against hydrogen peroxide(H2O2)-induced mitochondrial dysfunction and apoptosis in murine chondrocytic ATDC5 cells. We firstly determined mitochondrial dysfunction and apoptosis in ATDC5 cells which were exposed to H2O2. We then constructed an IGF-1-overexpressed adenovirus (IGF-1-Ad) harboring the IGF-1 coding sequence, and investigated the regulatory role of the overexpressed IGF-1 against the H2O2-induced mitochondrial dysfunction and apoptosis in ATDC5 cells. It was demonstrated that H2O2 treatment promoted the mitochondrial dysfunction, and further reduced the viability and induced apoptosis of ATDC5 cells. However, the IGF-1 overexpression by adenovirus inhibited the H2O2-induced mitochondrial dysfunction and further inhibited the H2O2-promoted apoptosis in ATDC5 cells. In conclusion, the present study found that oxidative stress promoted mitochondrial dysfunction and induced apoptosis in the murine chondrocytic ATDC5 cells, and the adenoviral vector-expressed IGF-1 protected the murine chondrocytic ATDC5 cells against such mitochondrial dysfunction and apoptosis. This study implies the protective role of IGF-1 against the oxidative stress in murine chondrocytic ATDC5 cells and demonstrates the promising anti-oxidative stress effect of the recombinant IGF-1-Ad against oxidative stress in chondrocytic cells.
Department of Orthopaedics, Tianjin 4th Centre Hospital, China.
Jinfeng
J
Wang
Wen
W
Cao
Futeng
F
Niu
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology*; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000009:adverse effects*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology*; D018384:Oxidative Stress / Q000235:genetics* / Q000502:physiology*
D007334:Insulin-Like Growth Factor I; D006861:Hydrogen Peroxide