Cell death in osteoarthritis.

To date, most studies examining cell death during the development of osteoarthritis (OA) have focused on death of chondrocytes and have primarily examined advanced stages of the disease. Very good evidence suggests that chondrocyte death does occur at some point in the pathogenesis of OA and that it can be due to apoptosis, necrosis, or some combination of the two. Chondrocyte death can be induced by mechanical injury, loss of extracellular matrix, loss of growth factors, or excessive levels of reactive oxygen species.

Differential calcium independent regulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases by interleukin-1beta and transforming growth factor-beta in Peyronie's plaque fibroblasts.

Purpose: Peyronie's disease is a fibrotic disorder of the tunica albuginea characterized by the localized formation of an inelastic plaque. We characterized matrix metalloproteinases and TIMPs (tissue inhibitors of matrix metalloproteinase) in Peyronie's disease tissue.

Materials And Methods: Matrix metalloproteinases and TIMPs were investigated in Peyronie's disease plaque tunica removed from patients with stable Peyronie's disease.

Endogenous production of reactive oxygen species is required for stimulation of human articular chondrocyte matrix metalloproteinase production by fibronectin fragments.

The objective of the present study was to determine if reactive oxygen species (ROS) are required as secondary messengers for fibronectin fragment-stimulated matrix metalloproteinase (MMP) production in human articular chondrocytes. Cultured cells were stimulated with 25 microg/ml of the alpha5beta1 integrin-binding 110-kDa fibronectin fragment (FN-f) in the presence and absence of various antioxidants including Mn(III) tetrakis(4-benzoic acid)porphyrin (MnTBAP). FN-f stimulation significantly increased intracellular levels of ROS in articular chondrocytes.

Chondrocyte cell death mediated by reactive oxygen species-dependent activation of PKC-betaI.

Signals generated by the extracellular matrix (ECM) promote cell survival. We have shown that chondrocytes detached from their native ECM and plated without serum at low density on poly-l-lysine undergo significant cell death that is associated with the production of reactive oxygen species (ROS). No cell death or ROS production was observed when cells were plated on fibronectin under the same conditions.

Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels.

Objective: To examine the role of oxidative stress in mediating cell death in chondrocytes isolated from the articular cartilage of young and old adult human tissue donors.

Methods: Cell death induced by the oxidant SIN-1 was evaluated in the alginate bead culture system using fluorescent probes to assess membrane integrity. Generation of peroxynitrite by the decomposition of SIN-1 was confirmed by positive immunostaining of treated cells for 3-nitrotyrosine.

Detection of nitrotyrosine in aging and osteoarthritic cartilage: Correlation of oxidative damage with the presence of interleukin-1beta and with chondrocyte resistance to insulin-like growth factor 1.

Objective: To determine whether oxidative damage to cartilage proteins can be detected in aging and osteoarthritic (OA) cartilage, and to correlate the results with the local production of interleukin-1beta (IL-1beta) and the responsiveness of isolated chondrocytes to stimulation with insulin-like growth factor 1 (IGF-1).

Methods: The presence of nitrotyrosine was used as a measure of oxidative damage. Histologic sections of knee articular cartilage, obtained from young adult and old adult cynomolgus monkeys, which develop age-related, naturally occurring OA, were evaluated.

The alpha5beta1 integrin provides matrix survival signals for normal and osteoarthritic human articular chondrocytes in vitro.

Objective: Chondrocyte cell death may play an important role in the development of arthritis. The goal of the present study was to evaluate the role of the extracellular matrix (ECM) in promoting chondrocyte survival via signals through the integrin family of ECM receptors.

Methods: Chondrocytes were isolated by sequential enzymatic digestion from normal ankle cartilage of organ donors and from osteoarthritic (OA) knee tissue obtained from patients undergoing total knee replacement.

Nitric oxide-mediated chondrocyte cell death requires the generation of additional reactive oxygen species.

Objective: Chondrocyte cell death, possibly related to increased production of endogenous nitric oxide (NO), has been observed during the pathogenesis of osteoarthritis and rheumatoid arthritis. The purpose of this study was to investigate the potential role of NO in causing chondrocyte cell death and to determine the contribution of other reactive oxygen species (ROS).

Methods: Cell death and cytotoxicity were evaluated in human articular chondrocytes in response to various NO donor compounds with and without agents that stimulate or inhibit the production of additional ROS using both the alginate bead and the monolayer culture systems.