Oxygen and reactive oxygen species in cartilage degradation: Friends or foes?
ABSTRACT This review is focused on the influence of oxygen and derived reactive species on chondrocytes aging, metabolic function and chondrogenic phenotype.
A systematic computer-aided search of the Medline database.
Articular cartilage is an avascular tissue, and consequently oxygen supply is reduced. Although the basal metabolic functions of the cells are well adapted to hypoxia, the chondrocyte phenotype seems to be oxygen sensitive. In vitro, hypoxia promotes the expression of the chondrogenic phenotype and cartilage-specific matrix formation, indicating that oxygen tension is probably a key parameter in chondrocyte culture, and particularly in the context of tissue engineering and stem cells transplantation. Besides the influence of oxygen itself, reactive oxygen species (ROS) play a crucial role in the regulation of a number of basic chondrocyte activities such as cell activation, proliferation and matrix remodeling. However, when ROS production exceeds the antioxidant capacities of the cell, an "oxidative stress" occurs leading to structural and functional cartilage damages like cell death and matrix degradation.
This paper is an overview of the in vitro and in vivo studies published on the influence of oxygen and derived reactive species on chondrocyte aging, metabolic function, and the chondrogenic phenotype. It shows, that oxygen and ROS play a crucial role in the control of cartilage homeostasis and that at this time, the exact role of "oxidative stress" in cartilage degradation still remains questionable.
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ABSTRACT: This study aimed to evaluate glycerol monooleate (GMO) as a carrier to develop viscoelastic and injectable sustained-release drug delivery systems. The potential pro- and antioxidant activity of the developed hydrolipidic gels were evaluated by measuring the production of ROS by polymorphonuclear leukocytes (PMNs). In addition, the biocompatibility and effectiveness of two selected gel candidates were evaluated in vivo by evaluating the benefit of a single intraarticular injection of these new treatments in a model of osteoarthritis in rabbits. The in vitro study demonstrated that the carrier F1 did not have a pro-oxidative effect and even protected PMNs against natural auto-activation, regardless of the incorporation of either clonidine chlorhydrate or betamethasone dipropionate. The in vivo study demonstrated that F1 and F1-BDP induced a loss of cartilage quality in comparison to the control and reference groups but that the lesions of cartilage observed were generally mild, with not much full-depth erosion. Moreover, no exacerbating inflammation was observed when considering the synovial membranes and the PGE2 and CRP levels. These results seemed to demonstrate that the sustained-release formulation based on GMO could be well-tolerated after intraarticular injection. Moreover, it could have the potential to prevent inflammatory conditions while sustaining drug activity locally over weeks. Copyright © 2015. Published by Elsevier B.V.International Journal of Pharmaceutics 04/2015; 490(1-2). DOI:10.1016/j.ijpharm.2015.04.064 · 3.79 Impact Factor
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ABSTRACT: Osteoarthritis (OA) is characterized by degradation of matrix and destruction of articular cartilage. Articular chondrocytes are solely responsible for the production and maintenance of the extracellular matrix. Therefore, chondrocyte disruption is implicated in cartilage degeneration. Numerous studies have shown that antioxidant treatments are promising therapeutics in cases of OA. This study was designedto examine whether vitamin E protects rat articular chondrocytes against increased inflammatory markers and oxidative stress and prevents cartilage destruction in mono-iodoacetate-induced osteoarthritis rat model. Data showed that osteoarthritis group showed a significant increase in inflammatory markers, Tumor Necrosis Factor-α (TNF-α) (38±1 ng/mL), Interlukin-6 (IL-6) (253±15 ng/mL) and oxidative stress marker, Super Oxide Dismutase (SOD) (14±1 ng/mL) compared to control (18±1 ng/mL), (121+/-23 ng/mL) and (8±1 ng/mL) respectively. Opposite trend was found when animals were treated with vitamin E where TNF-α (27±2 ng/mL) and SOD (10±1 ng/mL) declined significantly. Electro-microscopic examination documented the above results and showed improvement of knee joint after administration of vitamin E. This study supported the notion that OA is a multi factorial complication, caused by inflammation and increased oxidative stress. Administration of vitamin E decreased the markers of inflammation and oxidative stress as well asimproved ultra-structure of the knee jointin acute OA animal model. However, further work id needed to validate reliability in human patients suffering from osteoarthritis.American journal of pharmacology and toxicology 05/2014; 9(2):157-167,.