Proanthocyanidins-Mediated Nrf2 Activation Ameliorates Glucocorticoid-Induced Oxidative Stress and Mitochondrial Dysfunction in Osteoblasts.

Autor:	Chen L; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China.; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, China., Hu SL; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China.; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, China., Xie J; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China.; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, China., Yan DY; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China.; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, China., Weng SJ; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China., Tang JH; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China.; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, China., Wang BZ; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China.; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, China., Xie ZJ; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China., Wu ZY; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China., Yang L; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, Wenzhou 325000, China.; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, China.
Jazyk:	angličtina
Zdroj:	Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2020 Sep 25; Vol. 2020, pp. 9102012. Date of Electronic Publication: 2020 Sep 25 (Print Publication: 2020).
DOI:	10.1155/2020/9102012
Abstrakt:	The widespread use of therapeutic glucocorticoids has increased the frequency of glucocorticoid-induced osteoporosis (GIOP). One of the potential pathological processes of GIOP is an increased level of oxidative stress and mitochondrial dysfunction, which eventually leads to osteoblast apoptosis. Proanthocyanidins (PAC) are plant-derived antioxidants that have therapeutic potential against GIOP. In our study, a low dose of PAC was nontoxic to healthy osteoblasts and restored osteogenic function in dexamethasone- (Dex-) treated osteoblasts by suppressing oxidative stress, mitochondrial dysfunction, and apoptosis. Mechanistically, PAC neutralized Dex-induced damage in the osteoblasts by activating the Nrf2 pathway, since silencing Nrf2 partly eliminated the protective effects of PAC. Furthermore, PAC injection restored bone mass and promoted the expression of Nrf2 in the distal femur of Dex-treated osteoporotic rats. In summary, PAC protect osteoblasts against Dex-induced oxidative stress and mitochondrial dysfunction via the Nrf2 pathway activation and may be a promising drug for treating GIOP. Competing Interests: The authors have no conflicts of interest. (Copyright © 2020 Liang Chen et al.)
Databáze:	MEDLINE
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