Factors influencing the oxygen concentration gradient from the synovial surface of articular cartilage to the cartilage–bone interface: A modeling study

Abstract

Objective. There is very little information on the gradients of oxygen concentration from the synovial surface to the subchondral bone in articular cartilage. Cartilage is usually regarded as hypoxic, even though cellular metabolism is inhibited at low oxygen concentrations. We therefore measured rates of cellular consumption of oxygen and used these rates to calculate oxygen tension profiles across articular cartilage.Methods. The rate of oxygen consumption by bovine articular chondrocytes was measured in vitro, either in intact cartilage slices or in isolated chondrocytes. The oxygen tension profile across articular cartilage was predicted by solving a 1-dimensional reactiondiffusion equation. The effect of synovial fluid oxygen concentration, cell density, cartilage thickness, and influx of oxygen from the subchondral bone on the oxygen profile in the tissue was examined.Results. Oxygen consumption rates were relatively independent of oxygen tension at high oxygen tensions (5-21%), where they were ϳ10 nmoles/10 6 cells/hour for both isolated chondrocytes and for cartilage slices. Below 5% oxygen, the rate fell in an oxygen tension-dependent manner. Analysis showed that the oxygen profile across cartilage fell steeply in all but the thinnest cartilage samples but only fell to ϳ1% for low oxygen tensions in synovial fluid, with no supply from the subchondral bone. Conclusion.The oxygen tension in normal cartilage is not likely to fall to 1% except under abnormal conditions. Oxygen tensions within cartilage are strongly affected by a number of factors, including oxygen concentrations in synovial fluid, cartilage thickness, cell density, and cellular oxygen consumption rates. Supply from the subchondral bone may be of particular importance.

Oxygen consumption of equine articular chondrocytes: Influence of applied oxygen tension and glucose concentration during culture

“…But this was not the case, as the THP-1 cells showed a normal respiration pattern. Zhou et al (2004) found an oxygen uptake rate for chondrocytes of maximum 10.81 nmol/10 6 cells/h, corresponding to 180.16 pmol/min/ 10 6 , thus corresponding to aerobic cells like the thymic cells which consumed about 200 pmol 02/min/10 6 cells (Verlaet et al, 2002).…”

“…But Zhou et al (2004) worked on bovine articular cartilage from 18 to 24 months old steers without preliminary culture period at 5% O 2 tension and exposed the chondrocytes to 3 g/L glucose in the medium during oxymetry. Some authors used chondrocytes cell lines (Moulton et al, 1997), chondrocytes isolated from the ribs, the nasal septum (covered throughout the lifetime by the perichondrium), the growth plate or the intervertebral disc [known to have a PO 2 of only 2-8 mmHg in its deepest layers (Grimshaw and Mason, 2000)].…”

Notochordal intervertebral disc cells: Sensitivity to nutrient deprivation

“…O 2 measurements. Oxygen consumption rates (nmoles/ million cells/hour) were measured on cell suspensions using a Clark electrode in a sealed water-jacketed chamber (Strathkelvin Instruments, Glasgow, UK) (21). The pH did not fall during the 30-minute measurement period.…”

Unravelling the Role of Mechanical Stimuli in Regulating Cell Fate During Osteochondral Defect Repair

“…Oxygen consumption was modelled separately for each cell phenotype using Michealas-Menten kinetics [39][40][41] . In the equation shown, each phenotype was represented by n, whereby n = 1 represents MSCs; n = 2 represents CCs; n = 3 represents OBs; n = 4 represents FBs; n = 5 represents AB and; n = 6…”

“…In addition to this a constant oxygen boundary condition of 5 % was applied to the surface of the defect in order to simulate the nutrient supply from the synovial fluid 41,42 . Finally, based on the in silico study conducted by Zhou et al 41 , the following three assumptions were made: 1) The synovial fluid was well mixed and as such any gradients within the fluid were negligible 2) Oxygen transport was steady-state, meaning that the effects of mechanical loading and cartilage deformation on oxygen transport were ignored 3)…”