Requirement of the phosphatidylinositol 3-kinase/Akt signaling pathway for the effect of nicotine on interleukin-1beta-induced chondrocyte apoptosis in a rat model of osteoarthritis.
Chondrocyte apoptosis is mainly responsible for the progressive degeneration of cartilage in osteoarthritis (OA). Interleukin-1beta (IL-1β) was widely used as a modulating and chondrocyte apoptosis-inducing agent. Nicotine is able to confer resistance to apoptosis and promote cell survival in some cell lines, but its regulatory mechanism is ambiguous. We aimed to investigate the effect of nicotine on IL-1β-induced chondrocyte apoptosis and the mechanism underlying how nicotine antagonizes IL-1β-induced apoptosis of rat chondrocytes. Chondrocytes isolated from newborn rat joints were exposed to IL-1β. The cell viability was analyzed by the MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide) assay, and the apoptotic cells were counted with DAPI staining. The levels of Akt, phosphorylated-Akt (p-Akt) and downstream protein targets of Akt were detected by western blotting. The results showed that nicotine neutralized the effect of IL-1β on chondrocytes by activating PI3K/Akt signaling pathways, including the PI3K/Akt/Bcl-2 pathway, to block IL-1β-induced cell apoptosis and the PI3K/Akt/p70S6K (p70S6 kinase)/S6 pathway for promoting protein synthesis, modulating its downstream effectors such as TIMP-1 and MMP-13. Activation of the PI3K/Akt pathway is, in part, required for the effect of nicotine on IL-1β-induced chondrocyte apoptosis in a rat model of osteoarthritis.
Zhongshan Hospital, School of Medicine, University of Xiamen, Xiamen, Fujian, China.
Xinpeng
X
Zheng
Chun
C
Xia
Zhongyi
Z
Chen
Jiagu
J
Huang
Fengguang
F
Gao
Guideng
G
Li
Bing
B
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D010003:Osteoarthritis / Q000201:enzymology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism
D002867:Chromones; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D009538:Nicotine; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa