title: AGEs Induce Apoptosis in Rat Osteoblast Cells by Activating the Caspase-3 Signaling Pathway Under a High-Glucose Environment In Vitro.
abstract: Advanced glycation end products (AGEs) accumulate under high-glucose conditions and affect the healing of bone damage through various pathways; however, the detail mechanisms underlying these changes are unknown. In this study, we investigated the effects of AGEs on the apoptosis of in vitro-cultured rat osteoblasts under high-glucose conditions and explored the underlying mechanisms of these effects. First, we cultured rat osteoblasts and determined the accumulation of AGEs in the culture medium under high-glucose conditions. Then, we cultured rat osteoblasts under a high glucose concentration (35 mM), a normal glucose concentration (5.5 mM), and a normal glucose concentration (5.5 mM) in the presence of AGEs. We examined the effects of high glucose and AGEs on the apoptosis of rat osteoblasts at different time points and further analyzed the activity and changes in the levels of procaspase-3, caspase-3, and the caspase-3 substrate poly ADP-ribose polymerase (PARP). Finally, we added sRAGE (soluble RAGE) (an AGE inhibitor) or DEVD (a caspase-3 inhibitor) to each culture group and examined apoptosis under each culture condition and the changes in the levels of procaspase-3, caspase-3, and its substrate PARP. The results showed that the high-glucose condition and the addition of AGEs increased the apoptosis of rat osteoblast cells and simultaneously increased the activity and quantity of caspase-3. These increases could be inhibited by the AGE inhibitor sRAGE or the caspase-3 inhibitor DEVD. The above results demonstrate that high-glucose conditions lead to the accumulation of AGEs and activation of the caspase-3 signaling pathway, resulting in the increased apoptosis of cultured rat osteoblast cells.
authors.affiliation: Department of Oral and Cranio-Maxillofacial, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Shanghai, 200011, People's Republic of China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gynaecology and Obstetrics, Shanghai 1st Maternity and Infant Hospital, 536 Changle Road, Shanghai, 200040, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Oral and Cranio-Maxillofacial, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Shanghai, 200011, People's Republic of China.
authors.forename: Lunguo
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Oral and Cranio-Maxillofacial, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Shanghai, 200011, People's Republic of China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Oral and Cranio-Maxillofacial, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Shanghai, 200011, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Oral Implantology, Beijing Stomatological Hospital of Capital Medical University, Tian tan xi li 4, Beijing, 100050, People's Republic of China.
authors.forename: Pan
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Oral and Cranio-Maxillofacial, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Shanghai, 200011, People's Republic of China. braces_dr@hotmail.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Fang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D017127:Glycation End Products, Advanced; D053148:Caspase 3; D005947:Glucose
keywords: AGEs; Apoptosis; Caspase-3; High glucose; Osteoblasts