Oxygen, nitric oxide and articular cartilage

Abstract

Molecular oxygen is required for the production of nitric oxide (NO), a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O 2 , while the deep zone exists at less than 1% O 2 . Furthermore, oxygen tension can alter matrix synthesis, and the material properties of articular cartilage in vitro.The increase in nitric oxide associated with arthritis can be caused by pro-inflammatory cytokines and mechanical stress. Oxygen tension significantly alters endogenous NO production in articular cartilage, as well as the stimulation of NO in response to both mechanical loading and proinflammatory cytokines. Mechanical loading and proinflammatory cytokines also increase the production of prostaglandin E2 (PGE 2 ). There is a complex interaction between NO and PGE 2 , and oxygen tension can alter this interaction. These findings suggest that the relatively low levels of oxygen within the joint may have significant influences on the metabolic activity, and inflammatory response of cartilage as compared to ambient levels. A better understanding of the role of oxygen in the production of inflammatory mediators in response to mechanical loading, or pro-inflammatory cytokines, may aid in the development of strategies for therapeutic intervention in arthritis.

Effects of Flavangenol, an Extract of French Maritime Pine Bark on Collagen-Induced Arthritis in Rats

“…Thus, histopathlogical examination of the arthritic joints revealed that FG (1%) more markedly suppressed the articular lesions than ibuprofen (0.05%). NO is synthesized by the enzyme nitric oxide synthase (NOS) (25). NOS exists in three isoforms, neuronal (nNOS), inducible (iNOS) and endothelial nitric oxide synthase (eNOS), and the iNOS isoform is predominantly responsible for NO production in articular cartilage (25).…”

“…NO is synthesized by the enzyme nitric oxide synthase (NOS) (25). NOS exists in three isoforms, neuronal (nNOS), inducible (iNOS) and endothelial nitric oxide synthase (eNOS), and the iNOS isoform is predominantly responsible for NO production in articular cartilage (25). It is well known that NO produced by cartilage and synovial cells is implicated in the pathogenesis of human osteoarthritis and rheumatoid arthritis (26,27).…”

Solute Transport in Cyclically Deformed Porous Tissue Scaffolds with Controlled Pore Cross-Sectional Geometries

“…3,7 Under static conditions, nutrient transfer is governed by diffusion, that is, transport driven by a concentration gradient. However, diffusive transport is relatively slow (e.g., Fermor et al 8 reported diffusivities of approximately 2.5Â10 À7 cm 2 s À1 for uncharged dextrans in the surface zone of cartilage) and generally accounts for supplying cells at a depth of only a few hundred micrometers from the surface within a reasonable time. 9 In particular, for articular cartilage, which lacks a vascular bed, the notion arose that a pumping action due to joint mobility could contribute to cartilage nutrition.…”

Designing gradient plotted scaffolds as a tool for improving osteochondral regeneration

“…Measured oxygen tension in articular cartilage ranges from 7% (53 mm Hg) in the superficial layer to less than 1% (7.6 mm Hg) in the deep zone [72,73] of the oxygen tension of synovial fluid.…”