Effect of Low Oxygen Tensions on Glucose-Metabolizing Enzymes in Cultured Articular Chondrocytes

Marcus, Robert; Srivastava, V. M. L.

doi:10.3181/00379727-143-37349

Cited by 26 publications

(14 citation statements)

References 4 publications

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“…This is consistent with the commonly held view that articular chondrocytes maintain a high rate of glycolysis, even when cultured under atmospheric oxygen tensions (Marcus and Srivastava, 1973;Lane et al, 1977;Rajpurohit et al, 1996;Lee and Urban, 1997). However, the initial rates of lactate production were not maintained over the duration of the study by high cell density constructs (Fig.…”

Section: Discussionsupporting

confidence: 90%

“…However, early studies determined that the oxygen consumption rate of the chondrocyte is exceptionally low and this characteristic has since received little attention (Bywaters, 1937;Rosenthal et al, 1941). It has even been reported that the mitochondria of chondrocytes in situ lack certain cytochromes that are required for a fully functional electron transport chain (Mignotte et al, 1991) and that the apparatus for oxidative energy metabolism is only restored upon dedifferentiation of chondrocytes in monolayer (Marcus and Srivastava, 1973;Benel et al, 1986).…”

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confidence: 99%

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Rate of oxygen consumption by isolated articular chondrocytes is sensitive to medium glucose concentration

Heywood

Bader

Lee

2005

Journal Cellular Physiology

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Cartilage tissue engineering typically involves the culture of isolated chondrocytes within a scaffold material. The oxygen tension within the engineered tissue is known to be an essential parameter for implant success. This will be sensitive to the oxygen consumption behavior of the embedded chondrocytes, which remains to be characterized. We report that the oxygen consumption of bovine articular chondrocytes is sensitive to glucose deprivation below 2.7 mM, increasing from a basal level of 9.6x10(-16) to <18.4x10(-16) mol/cell.h in 1.3 mM glucose. Further studies examined the influence of selecting high (18.4 mM) or low (5.1 mM) glucose medium on the oxygen tension in 2 mm thick cellular agarose constructs. A relative upregulation of oxygen consumption was observed in constructs cultured in low glucose medium. This resulted in the near-anoxic oxygen concentration of 5 microM oxygen in constructs seeded with 40x10(6) cells/ml, compared to 57 microM in the corresponding high glucose culture. The upregulation of oxygen consumption generally corresponded to the inhibition of glycolysis, which is consistent with the Crabtree phenomenon. Medium osmolarity (316-600 mOsm) had minimal effects on chondrocyte oxygen consumption rate. In conclusion, glucose availability is a critical parameter that regulates the oxygen tension within tissue engineered constructs.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Rate of oxygen consumption by isolated articular chondrocytes is sensitive to medium glucose concentration

Heywood

Bader

Lee

2005

Journal Cellular Physiology

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“…Tissue engineering simulations of a patella-sized construct used the measured glucose consumption rate of 1.24 ± 0.35 × 10 −13 mol cell −1 hr −1 and a glucose threshold of 12.5 mM (Supplementary Material), values consistent with prior reports (Marcus and Srivasta, 1973; Obradovic et al, 1999). The large construct model predicted glucose concentrations within the construct interior falling below the 12.5 mM threshold for the majority of the time in culture (Figure 7A, B, C).…”

Section: Resultssupporting

confidence: 68%

Synthesis rates and binding kinetics of matrix products in engineered cartilage constructs using chondrocyte-seeded agarose gels

Nims

Cigáň

Albro

et al. 2014

Journal of Biomechanics

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Large-sized cartilage constructs suffer from inhomogeneous extracellular matrix deposition due to insufficient nutrient availability. Computational models of nutrient consumption and tissue growth can be utilized as an efficient alternative to experimental trials to optimize the culture of large constructs; models require system-specific growth and consumption parameters. To inform models of the [bovine chondrocyte]-[agarose gel] system, total synthesis rate (matrix accumulation rate + matrix release rate) and matrix retention fractions of glycosaminoglycans (GAG), collagen, and cartilage oligomeric matrix protein (COMP) were measured either in the presence (continuous or transient) or absence of TGF-β3 supplementation. TGF-β3’s influence on pyridinoline content and mechanical properties was also measured. Reversible binding kinetic parameters were characterized using computational models. Based on our recent nutrient supplementation work, we measured glucose consumption and critical glucose concentration for tissue growth to computationally simulate the culture of a human patella-sized tissue construct, reproducing the experiment of Hung et al., (2003). Transient TGF-β3 produced the highest GAG synthesis rate, highest GAG retention ratio, and highest binding affinity; collagen synthesis was elevated in TGF-β3 supplementation groups over control, with the highest binding affinity observed in the transient supplementation group; both COMP synthesis and retention were lower than those for GAG and collagen. These results informed the modeling of GAG deposition within a large patella construct; this computational example was similar to previous experimental results without further adjustments to modeling parameters. These results suggest that these nutrient consumption and matrix synthesis models are an attractive alternative for optimizing the culture of large-sized constructs.

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“…Chondrocytes may exist under low oxygen tension, and they metabolize glucose primarily by glycolysis (Stockwell, 1979). This anaerobic metabolic pathway is maintained even under aerobic conditions (Marcus and Srivastava, 1973). Therefore, it seems conceivable, that increased rates of mRNAs encoding glycolytic enzymes in recombinant Bmp-2 expressing C3H10T 1 ⁄2 cells might reflect the development along the chondrogenic lineage.…”

Section: Bmp-2-mediated Up-regulation Of Genes Encoding Glycolytic Enmentioning

confidence: 99%

Bmp‐2 downstream targets in mesenchymal development identified by subtractive cloning from recombinant mesenchymal progenitors (C3H10T½)

Bächner¹,

Ahrens²,

Schröder³

et al. 1998

Dev. Dyn.

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A Bmp-dependent in vitro model was used to identify cDNAs during the manifestation of mesenchymal lineages. This model involves the recombinant expression of Bmps (Bmp-2, Bmp-4-7) in murine mesenchymal C3H10T 1 ⁄2 progenitors, which leads to the differentiation into three lineages: the osteogenic, the chondrogenic and the adipogenic lineage, albeit in varying efficiencies. By subtractive cloning, 21 Bmp-2-regulated cDNAs from C3H10T 1 ⁄2 mesenchymal progenitors were identified; 20 were related to known sequences and 1 was not. During mouse embryonic development, many of these cDNAs are expressed in chondrogenic, osteogenic, and in adipogenic tissues. Novel findings include a G 0 /G 1 switch gene (G0S2), which was demonstrated to be predominantly expressed in adipose tissue during late murine embryonic development. Furthermore, the membrane-standing glycoprotein autotaxin (ATX) is expressed, at precartilage condensations, joint regions, and during tooth development. An as yet undescribed cDNA, 29A, which encodes a putative secreted factor, is expressed in developing osteo-/chondrogenic tissues of vertebrae, ribs, tooth, and the limb bud. C3H10T 1 ⁄2-progenitors, therefore, may serve as a legitimate model for the investigation of the Bmp-mediated events during mesenchymal differentiation. Dev. Dyn. 1998;213:398-411.1998 Wiley-Liss, Inc.

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Effect of Low Oxygen Tensions on Glucose-Metabolizing Enzymes in Cultured Articular Chondrocytes

Cited by 26 publications

References 4 publications

Rate of oxygen consumption by isolated articular chondrocytes is sensitive to medium glucose concentration

Rate of oxygen consumption by isolated articular chondrocytes is sensitive to medium glucose concentration

Synthesis rates and binding kinetics of matrix products in engineered cartilage constructs using chondrocyte-seeded agarose gels

Bmp‐2 downstream targets in mesenchymal development identified by subtractive cloning from recombinant mesenchymal progenitors (C3H10T½)

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