Vitamin E protects rat mesenchymal stem cells against hydrogen peroxide-induced oxidative stress in vitro and improves their therapeutic potential in surgically-induced rat model of osteoarthritis

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• 作者：F.U. Bhatti^&dagger ; ; ^&Dagger ; ; ^{fbhatti@uthsc.edu} ; A. Mehmood^&dagger ; ; ^{azra_mehmood@hotmail.com} ; N. Latief^&dagger ; ; ^{noreenlatief@gmail.com} ; S. Zahra^&dagger ; ; ^{sanazaahra@gmail.com} ; H. Cho^&Dagger ; ; ^§ ; ; ^{hcho4@uthsc.edu} ; S.N. Khan^&dagger ; ; ^{snkhan50@yahoo.com} ; S. Riazuddin^&dagger ; ; ^‖ ; ^{riazuddin@aimrc.org}
• 关键词：Osteoarthritis ; Mesenchymal stem cells ; Antioxidant ; Vitamin E ; Oxidative stress
• 刊名：Osteoarthritis and Cartilage
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：25
• 期：2
• 页码：321-331
• 全文大小：2929 K
• 卷排序：25

文摘

Oxidative stress is a major obstacle against cartilage repair in osteoarthritis (OA). Anti-oxidant agents can play a vital role in addressing this issue. We evaluated the effect of Vitamin E preconditioning in improving the potential of mesenchymal stem cells (MSCs) to confer resistance against oxidative stress prevailing during OA.MethodsVitamin E pretreated MSCs were exposed to oxidative stress in vitro by hydrogen peroxide (H2O2) and also implanted in surgically-induced rat model of OA. Analysis was done in terms of cell proliferation, apoptosis, cytotoxicity, chondrogenesis and repair of cartilage tissue.ResultsVitamin E pretreatment enabled MSCs to counteract H2O2-induced oxidative stress in vitro. Proliferative markers, proliferating cell nuclear antigen (PCNA) and Ki67 were up-regulated, along with the increase in the viability of MSCs. Expression of transforming growth factor-beta (TGFβ) was also increased. Reduction of apoptosis, expression of vascular endothelial growth factor (VEGF) and caspase 3 (Casp3) genes, and lactate dehydrogenase (LDH) release were also observed. Transplantation of Vitamin E pretreated MSCs resulted in increased proteoglycan contents of cartilage matrix. Increased expression of chondrogenic markers, Aggrecan (Acan) and collagen type-II alpha (Col2a1) accompanied by decreased expression of collagen type-I alpha (Col1a1) resulted in increased differentiation index that signifies the formation of hyaline cartilage. Further, there was an increased expression of PCNA and TGFβ genes along with a decreased expression of Casp3 and VEGF genes with increased histological score.ConclusionTaken together results of this study demonstrated that Vitamin E pretreated MSCs have an improved ability to impede the progression of OA and thus increased potential to treat OA.