Osteoarthritis Cartilage. 2016 Sep 30. pii: S1063-4584(16)30294-1. doi: 10.1016/j.joca.2016.09.014. [Epub ahead of print]

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.

Bhatti FU¹, Mehmood A², Latief N³, Zahra S⁴, Cho H⁵, Khan SN⁶, Riazuddin S⁷.

Abstract

OBJECTIVE:

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.

METHODS:

Vitamin 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.

RESULTS:

Vitamin 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.

CONCLUSION:

Taken 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.

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