Combination of reduced oxygen tension and intermittent hydrostatic pressure: a useful tool in articular cartilage tissue engineering

Hansen, U.; Schünke, Michael; Domm, Christian; Ioannidis, Niki; Hassenpflug, J.; Gehrke, Thorsten; Kurz, Bodo

doi:10.1016/s0021-9290(01)00050-1

Cited by 127 publications

(85 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6A). Moreover, in accordance with a previous study on articular chondrocytes (Hansen et al, 2001), we measured strongly increased concentrations of type-II collagen in wild-type cultures under hypoxia compared with normoxia (Fig. 6B).…”

Section: E) Hif-1α In Epiphyseal Chondrocytessupporting

confidence: 92%

HIF-1α controls extracellular matrix synthesis by epiphyseal chondrocytes

Pfander

Cramer

Schipani

et al. 2003

Journal of Cell Science

229

205

View full text Add to dashboard Cite

The transcription factor HIF-1α plays a crucial role in modifying gene expression during low oxygen tension. In a previous study, we demonstrated that HIF-1α is essential for chondrocyte growth arrest and survival in vivo. To explore further the role of HIF-1α in cartilage biology, we undertook studies with primary epiphyseal chondrocytes with a targeted deletion of HIF-1α. In this study, we show that HIF-1α is necessary for regulating glycolysis under aerobic and anaerobic conditions. HIF-1α-null chondrocytes were unable to maintain ATP levels in hypoxic microenvironments, indicating a fundamental requirement for this factor for the regulation of chondrocyte metabolism. Synthesis of the angiogenic factor vascular endothelial growth factor was also significantly induced by hypoxia,and this increase is lost in HIF-1α-null mutant cells. Under hypoxic conditions, aggrecan mRNA and protein levels were significantly reduced in chondrocytes lacking the HIF-1α transcription factor. Interestingly,strongly increased type-II collagen protein levels were detected in wild-type cells after 44 hours of hypoxia. In addition, type-II collagen mRNA and protein levels were strongly decreased under low oxygen in chondrocytes lacking HIF-1α. In summary, our results clearly demonstrate the importance of HIF-1α in maintenance of anaerobic glycolysis, and thereby extracellular matrix synthesis, of epiphyseal chondrocytes.

show abstract

Section: E) Hif-1α In Epiphyseal Chondrocytessupporting

confidence: 92%

HIF-1α controls extracellular matrix synthesis by epiphyseal chondrocytes

Pfander

Cramer

Schipani

et al. 2003

Journal of Cell Science

229

205

View full text Add to dashboard Cite

show abstract

“…The oxygen concentrations used in the present study were based on the predicted concentration within articular cartilage tissue in vivo in the range of 1%-5% 12 and on previous reports investigating the influence of oxygen on chondrocyte function. 15,17,28 The metabolic status of fresh chondrocytes and of the cells after expansion was characterized by determining the activities of citrate synthase, a mitochondrial marker enzyme (aerobic metabolism), 29 and lactate dehydrogenase, the terminal enzyme of glycolysis (anaerobic metabolism). The transcriptional activity was assessed using real-time PCR.…”

Section: Experimental Designmentioning

confidence: 99%

Hypoxic expansion promotes the chondrogenic potential of articular chondrocytes

Egli

Bastian

Ganz

et al. 2008

Journal Orthopaedic Research

View full text Add to dashboard Cite

For cell-based cartilage repair strategies, an ex vivo expansion phase is required to obtain sufficient numbers of cells needed for therapy. Although recent reports demonstrated the central role of oxygen for the function and differentiation of chondrocytes, a beneficial effect of low oxygen concentrations during the expansion of the cells to further improve their chondrogenic capacity has not been investigated. Therefore, freshly harvested bovine articular chondrocytes were grown in two-dimensional monolayer cultures at 1.5% and 21% O 2 and redifferentiation was subsequently induced in three-dimensional micromass cultures at 1.5%, 5%, and 21% O 2 . Cells expanded at 1.5% O 2 were characterized by low citrate synthase (aerobic energy metabolism)-and high LDH (anaerobic energy metabolism)-activities, suggesting an anaerobic energy metabolism. Collagen type II mRNA was twofold higher in cells expanded at 1.5% as compared to expansion at 21% O 2 . Micromass cultures grown at 21% O 2 showed up to a twofold increase in the tissue content of glycosaminoglycans when formed with cells expanded at 1.5% instead of 21% O 2 . However, no differences in the levels of transcripts and in the staining for collagen type II protein were observed in these micromass cultures. Hypoxia (1.5% and 5% O 2 ) applied during micromass cultures gave rise to tissues with low contents of glycosaminoglycans only. In vivo, the chondrocytes are adapted to a hypoxic environment. Taking this into account, by applying 1.5% O 2 in the expansion phase in the course of cell-based cartilage repair strategies, may result in a repair tissue with higher quality by increasing the content of glycosaminoglycans. ß

show abstract

“…BAChs seeded into collagen scaffolds accumulated 3.1 times more GAG when subjected to static HP at 2.8 MPa [94]. Oscillating HP (OHP) range from 0.1 to 10 MPa at frequencies ranging from 0.01 to 1 Hz [95][96][97][98][99]. One study found hBMSC pellets subjected to 10 MPa OHP at 1 Hz for 14 days expressed twice as much Col II and ACAN [100].…”

Section: Non-conventional Bioreactorsmentioning

confidence: 99%