Die Konzeption von Kompression, Hypoxie und konsekutiver Mucopolysaccharidbildung in der Kausalen Analyse der Chondrogenese

Krompecher, S; Tóth, L

doi:10.1007/bf00523585

Cited by 9 publications

(3 citation statements)

References 18 publications

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“…Previously, Pauwels proposed that hydrostatic pressure, developing during compressive loading of tissues, is the specific stimulus to induce formation of cartilaginous matrix in the body (Pauwels, 1980). Krompecher later proposed that the hydrostatic pressure generated during mechanical loading forces vessels closed by overcoming blood pressure; this reduces blood supply to related tissues and results in a hypoxic environment that is instead the specific chondrogenic stimulus (Krompecher and Tóth, 1964). The outcomes of experiment I indicate that mechanical loading can be a direct promoter of cartilage-related gene expression independently of low oxygen.…”

Section: Discussionmentioning

confidence: 99%

Mechano-Hypoxia Conditioning of Engineered Human Meniscus

Szojka

Sopcak

et al. 2021

Front. Bioeng. Biotechnol.

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Meniscus fibrochondrocytes (MFCs) experience simultaneous hypoxia and mechanical loading in the knee joint. Experimental conditions based on these aspects of the native MFC environment may have promising applications in human meniscus tissue engineering. We hypothesized that in vitro “mechano-hypoxia conditioning” with mechanical loading such as dynamic compression (DC) and cyclic hydrostatic pressure (CHP) would enhance development of human meniscus fibrocartilage extracellular matrix in vitro. MFCs from inner human meniscus surgical discards were pre-cultured on porous type I collagen scaffolds with TGF-β3 supplementation to form baseline tissues with newly formed matrix that were used in a series of experiments. First, baseline tissues were treated with DC or CHP under hypoxia (HYP, 3% O2) for 5 days. DC was the more effective load regime in inducing gene expression changes, and combined HYP/DC enhanced gene expression of fibrocartilage precursors. The individual treatments of DC and HYP regulated thousands of genes, such as chondrogenic markers SOX5/6, in an overwhelmingly additive rather than synergistic manner. Similar baseline tissues were then treated with a short course of DC (5 vs 60 min, 10–20% vs 30–40% strain) with different pre-culture duration (3 vs 6 weeks). The longer course of loading (60 min) had diminishing returns in regulating mechano-sensitive and inflammatory genes such as c-FOS and PTGS2, suggesting that as few as 5 min of DC was adequate. There was a dose-effect in gene regulation by higher DC strains, whereas outcomes were inconsistent for different MFC donors in pre-culture durations. A final set of baseline tissues was then cultured for 3 weeks with mechano-hypoxia conditioning to assess mechanical and protein-level outcomes. There were 1.8–5.1-fold gains in the dynamic modulus relative to baseline in HYP/DC, but matrix outcomes were equal or inferior to static controls. Long-term mechano-hypoxia conditioning was effective in suppressing hypertrophic markers (e.g., COL10A1 10-fold suppression vs static/normoxia). Taken together, these results indicate that appropriately applied mechano-hypoxia conditioning can support meniscus fibrocartilage development in vitro and may be useful as a strategy for developing non-hypertrophic articular cartilage using mesenchymal stem cells.

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Section: Discussionmentioning

confidence: 99%

Mechano-Hypoxia Conditioning of Engineered Human Meniscus

Szojka

Sopcak

et al. 2021

Front. Bioeng. Biotechnol.

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“…T h e vascular system, in turn, may act by producing ischaemia or through the anoxia produced as a result of ischaemia. Krompecher & Toth (1964) have related cartilage formation, at sites of compression, to a local constriction of the blood vessels, consequent local hypoxia, and an adaptation of the cells to the hypoxia by increased acid mucopolysaccharide synthesis. The acid mucopolysaccharides are the major macromolecule secreted by the chondroblasts and chondrocytes, and in this study we begin to see a possible mechanism whereby the cells adapt to the environmental change .…”

Section: Less Thanmentioning

confidence: 99%

“…Adaptation of the cells of bone to compression and the resulting increased acid mucopolysaccharide synthesis and chondrogenesis has been advocated by Krompecher & Toth (1964). Some unknown metabolic adaptation is what they envisage.…”

Section: -646)mentioning

confidence: 99%

Cellular Differentiation in Skeletal Tissues

Hall

1970

Biological Reviews

135

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The effect of low oxygen concentration on growth, glycolysis, and sulfate incorporation by articular chondrocytes in monolayer culture

Marcus

Sokoloff

1973

Arthritis & Rheumatism

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Radiosulfate incorporation, DNA synthesis, and glycoiysis by rabbit articular chondrocytes and skin fibrocytes in monolayer culture were compared under different concentrations of oxygen (19,6.8, 1.3, and 0.6%). Cell for cell, chondrocytes under each condition had higher levels of radiosulfate incorporation and giycoiysis than did fibrocytes. Growth of the fibrocytes was reduced approximately 20% when the oxygen concentration was reduced to 6.8%. but that of chondrocytes was unaffected. A progressive Pasteur effect was observed with both cell types. Radiosulfate incorporation was reduced at low oxygen concentrations. The findings in this cell culture system are thus at variance with other published evidence that hypoxia is a major histogenetic force favoring chondrogenic expression.Articular cartilage, being an avascular tissue, must somehow adapt itself to its anaerobic environment in order to survive, grow, and produce extracellular matrix in vim. T w o of these adaptations, a high rate of anaerobic glycolysis and a low rate of oxygen consumption, were described originally by investigators studying cartilage slices (1, 2). A variety of evidence, furthermore, suggests that low oxygen tension independently or in conjunction with other factors might play an important role in the differentiation of cartilage by enhancing its production of extracellular matrix (acid mucopolysaccharides) (3-This study was undertaken to investigate (a) whether low oxygen tensions are a measurable 10). Submitted for publication Nov. 8, 1972; accepted May 30. 1973. force in the differentiation of articular chondrocytes grown in monolayer culture, and (b) whether the cultured chondrocytes retain the high rate of glycolysis characteristic of whole cartilage. METHODS AND MATERIALS Technique of CultureThe articular chondrocytes and cutaneous fibrocytes were isolated from 6-to 8-week-old New Zealand white rabbits by a method described elsewhere (1 1). The cells (100,000 to 300,000) were inoculated into 75 sq cm plastir Falcon flasks (Falcon Plastic Co., Los Angeles, Calif.) containing 12 ml of Ham's F12 medium (Grand Island Biological Co., Grand Island, N.Y.) supplemented with 10% fetal calf serum (Grand Island) and streptomycin-penicillin (LO &ml and 10 units/ml, respectively). The cells were fed three times a week and gassed with 90% air:lO% C02. When the cells became confluent (generally on the eighth day), Dulbecco's modified Eagle's medium (DMEM) (Grand Island) was substituted for the F12 medium. On the 1 Ith day the cells were trypsinized, and 100,000 to 200,000 cells were inoculated into 6 0 x 15 mm glass petri dishes containing 4 ml of supplemented DMEM. The dishes were placed in anaerobic culture jars which were gassed and incubated at 37O. They were refed and gassed on Day 2. On Day 4 the medium was replaced by supplemented DMEM in which MgSO, was replaced by MgCI,, 165 mg/liter. On

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Die Konzeption von Kompression, Hypoxie und konsekutiver Mucopolysaccharidbildung in der Kausalen Analyse der Chondrogenese

Cited by 9 publications

References 18 publications

Mechano-Hypoxia Conditioning of Engineered Human Meniscus

Mechano-Hypoxia Conditioning of Engineered Human Meniscus

Cellular Differentiation in Skeletal Tissues

The effect of low oxygen concentration on growth, glycolysis, and sulfate incorporation by articular chondrocytes in monolayer culture

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