Abstract:
:Advanced glycation end products (AGEs) can stimulate osteoblast apoptosis and have a critical role in the pathophysiology of diabetic osteoporosis. Mitochondrial abnormalities are closely related to osteoblast dysfunction. However, it remains unclear whether mitochondrial abnormalities are involved in AGE-induced osteoblastic cell apoptosis. Silibinin, a major flavonolignan compound of silimarin, has strong antioxidant and mitochondria-protective properties. In the present study, we explored the possible mitochondrial mechanisms underlying AGE-induced apoptosis of osteoblastic cells and the effect of silibinin on osteoblastic cell apoptosis. We demonstrated that mitochondrial abnormalities largely contributed to AGE-induced apoptosis of osteoblastic cells, as evidenced by enhanced mitochondrial oxidative stress, conspicuous reduction in mitochondrial membrane potential and adenosine triphosphate production, abnormal mitochondrial morphology, and altered mitochondrial dynamics. These AGE-induced mitochondrial abnormalities were mainly mediated by the receptor of AGEs (RAGE). In addition, we found that silibinin directly downregulated the expression of RAGE and modulated RAGE-mediated mitochondrial pathways, thereby preventing AGE-induced apoptosis of osteoblastic cells. This study not only provides a new insight into the mitochondrial mechanisms underlying AGE-induced osteoblastic cell apoptosis, but also lays a foundation for the clinical use of silibinin for the prevention or treatment of diabetic osteoporosis.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Mao YX,Cai WJ,Sun XY,Dai PP,Li XM,Wang Q,Huang XL,He B,Wang PP,Wu G,Ma JF,Huang SBdoi
10.1038/s41419-018-0718-3subject
Has Abstractpub_date
2018-06-04 00:00:00pages
674issue
6issn
2041-4889pii
10.1038/s41419-018-0718-3journal_volume
9pub_type
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