Henrotin Y, Kurz B, Aigner T. Oxygen and reactive oxygen species in cartilage degradation: friends or foes?

Bone and Cartilage Research Unit, University of Liège, Institute of Pathology, Level +5, CHU Sart-Tilman, 4000 Liège, Belgium.
Osteoarthritis and Cartilage (Impact Factor: 4.17). 09/2005; 13(8):643-54. DOI: 10.1016/j.joca.2005.04.002
Source: PubMed


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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Available from: Yves Henrotin, Aug 31, 2015
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    • "The second challenged formulation is a newly synthesized chemically modified HA grafted with antioxidant moieties, which has proven to resist in vitro oxidative stress such as found in OA articulations and proven to be biocompatible [14] [15] [16]. The addition of an antioxidant could be beneficial for HA protection leading to a longer acting formulation but also for its intrinsic antioxidant activity known to be beneficial for OA pathology [17]. "
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    ABSTRACT: http://authors.elsevier.com/a/1RlS~3Lfa~u4j8 Viscosupplementation (VS) is a therapy for osteoarthrosis (OA) consisting of repetitive intra- articular injections of hyaluronic acid (HA). It is known to be clinically effective in relieving pain and increasing joint mobility by restoring joint homeostasis. In this study, the effects of two novel HA-based VS hydrogel formulations were assessed and challenged against a pure HA commercial formulation for the first time and this in a rabbit model of early OA induced by anterior cruciate ligament transection (ACLT). The first formulation tested was a hybrid hydrogel composed of HA and reacetylated chitosan, a biopolymer considered to be chondroprotective, assembled thanks to an ionic shielding. The second formulation consisted of a novel HA polymer grafted with antioxidant molecules (HA-4AR) aiming at decreasing OA oxidative stress and increasing HA retention time in the articulation. ACLT was performed on rabbits in order to cause structural changes comparable to traumatic osteoarthrosis. The protective effects of the different formulations were observed on the early phase of the pathology in a full randomized and blinded manner. The cartilage, synovial membrane, and subchondral bone were evaluated by complementary investigation techniques such as gross morphological scoring, scanning electron microscopy, histological scoring, and micro-computed tomography were used. In this study, ACLT was proven to successfully reproduce early OA articular characteristics found in humans. HA and HA-4AR hydrogels were found to be moderately protective for cartilage as highlighted by μCT. The HA-4AR was the only formulation able to decrease synovial membrane hypertrophy occurring in OA. Finally, the hybrid HA-reacetylated chitosan hydrogel surprisingly led to increased subchondral bone bone remodeling and cartilage defect formation. This study shows significant effects of two innovative HA modification strategies in an OA rabbit model, which warrant further studies towards more effective viscosupplementation formulations.
    European Journal of Pharmaceutics and Biopharmaceutics 10/2015; 96:388-395. DOI:10.1016/j.ejpb.2015.09.005 · 3.38 Impact Factor
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    • "Nowadays, there is increasing interest in the potential role that synovial inflammation may play in the pathogenesis of this very common form of arthritis. In this respect, reactive oxygen species (ROS) and pro-inflammatory cytokines produced in OA by the synovium and chondrocytes are proved to be key players in the degradation of cartilage (Goodwin et al., 2010; Henrotin et al., 2005; Martin et al., 2009; Ramakrishnan et al., 2010). Currently, the usual pharmacological approaches to targeting relief of pain and inflammation (non-steroidal anti-inflammatory drugs and opioids) are highly restricted because of severe systemic side effects with long-term use (Zhang et al., 2010). "
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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 · 3.65 Impact Factor
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    • "Tissue inhibitor of metalloproteinase (TIMP)-1 is also produced by synovial tissue [26]. The reactive oxygen species (ROS) have been described as key factors involved in cartilage pathogenesis of OA [58] [59]. They are also produced by the synovial tissue [60]. "

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