Aluminum induces osteoblast apoptosis through the oxidative stress-mediated JNK signaling pathway.
Aluminum (Al) is considered to be a potentially toxic metal. Al exposure inhibits bone formation. Few studies have investigated the mechanism of inhibitory effects of Al on bone formation. Thus, in this study, osteoblasts were cultured and exposed to different concentrations of Al to investigate the mechanism behind the inhibitory effects of Al on bone formation. Al-treated osteoblasts showed signs of oxidative stress and a high apoptosis rate. The levels of osteoblasts activity markers (bone gamma-carboxyglutamic acid protein and bone alkaline phosphatase) were significantly lower in the Al-treated groups than in the control group. The c-Jun N-terminal kinase (JNK), a major signaling pathway in regulating cell apoptosis, was activated. The phosphorylation state of JNK was significantly increased. The mRNA and protein expression of c-Jun were both significantly upregulated. The pro-apoptotic genes (caspase 3, caspase 9, bax, and factor-related apoptosis ligand) were significantly increased. However, Bcl-2, an anti-apoptotic gene, was significantly decreased. In conclusion, the results of this study indicate that Al induces osteoblast apoptosis by activating the oxidative stress-mediated JNK pathway, which causes cell injuries and reduces the number and function of osteoblasts, thereby inhibiting bone formation.
College of Animal Science and Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
Xinwei
X
Li
Yanfei
Y
Han
Yuan
Y
Guan
Liang
L
Zhang
Chongsheng
C
Bai
Yanfei
Y
Li
D000469:Alkaline Phosphatase / Q000378:metabolism; D000535:Aluminum / Q000494:pharmacology* / Q000633:toxicity; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D012886:Skull / Q000166:cytology / Q000254:growth & development; D015854:Up-Regulation / Q000187:drug effects*
D017607:Aluminum Compounds; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D002712:Chlorides; D015675:Osteocalcin; D000077410:Aluminum Chloride; D000535:Aluminum; D000469:Alkaline Phosphatase