Receptor-mediated glucocorticoid inhibition of cell proliferation in mouse growth cartilage in vitro

Silbermann, Michael; Maor, Gila

doi:10.1530/acta.0.1080343

Cited by 18 publications

(6 citation statements)

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“…The maximally effective concentration and the ED 50 for the stimulation were consistent with the DEX effect being mediated by glucocorticoid receptors, which are present in chondrogenic cells (34)(35)(36). The cartilage nodules that formed in the presence of DEX were larger than those formed in its absence, and new nodules developed in discrete areas of the documented suppression by glucocorticoids of markers for the cartilage phenotype, both in vitro and in vivo (12,36,37).…”

Section: Discussionsupporting

confidence: 53%

Effects of Dexamethasone and Vitamin D₃on Cartilage Differentiation in a Clonal Chondrogenic Cell Population

1989

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We have investigated the regulation of chondroblast/chondrocyte differentiation using a unique clonal cell population, designated RCJ 3.1C5 (C5), which differentiates into discrete three-dimensional cartilage nodules when grown in the presence of 15% fetal calf serum. Histologically, the nodules resembled hyaline cartilage; they contained large rounded chondrocytes surrounded by a refractile matrix which stained intensely with Alcian blue, exhibited metachromasia after Toluidine blue staining, and stained with an antibody against type II collagen. The cartilage nodules that formed did not mineralize, despite the presence of organic phosphate in the culture medium. The synthetic glucocorticoid dexamethasone (DEX) increased the number of cartilage nodules formed in a dose-dependent manner (ED50, approximately 10(-9) M), with a maximal stimulatory dose of 10(-8) M. DEX had no effect on the population doubling time and saturation density. The effects of DEX on the number of cartilage nodules were similar whether it was added from the beginning of the culture period (starting during exponential growth) or at confluence. In contrast, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited cartilage nodule formation in a dose-dependent manner (IC50, approximately 5 x 10(-10) M), with maximum inhibition at 10(-7) M. In addition, 1,25-(OH)2D3 decreased cell proliferation and saturation density. Equimolar doses of the vitamin D3 metabolites 24,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 had no effect. C5 cells treated with 1,25-(OH)2D3 in the absence of DEX during the exponential growth phase exhibited a reduced capacity to form cartilage nodules upon subsequent exposure to DEX. At confluence, before cartilage nodules had formed, C5 cells responded to PTH and prostaglandin-E2 with increases in intracellular cAMP of about 10- and 95-fold respectively. After cartilage nodules were present, prostaglandin-E2 responsiveness decreased to about 25-fold, whereas there was no significant change in PTH responsiveness. DEX decreased the population alkaline phosphatase levels at all times measured, whereas 1,25-(OH)2D3 had a biphasic effect: an increase at 5 days in culture, followed by a decrease at later times in culture. These data indicate that the clonal cell line RCJ 3.1C5 is a useful model system in which to investigate cartilage differentiation.

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Section: Discussionsupporting

confidence: 53%

Effects of Dexamethasone and Vitamin D₃on Cartilage Differentiation in a Clonal Chondrogenic Cell Population

1989

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“…IGF-1 and glucocorticoids have synergistic effects on chondrocytes (Itagane et al, 1991). The effects of glucocorticoids on chondrocytes may be direct or via regulation of production of inflammatory mediators (Blondelon et al, 1980;Sheppard et al, 1982;Steinberg & Sledge, 1983;Silbermann & Maor, 1985;Shinmei et al, 1988;Di Battista et al, 1991;Itagane et al, 1991;Price et al, 1992;Schlaghecke et al, 1992).…”

Section: Effect Of Growth Factors and Glucocorticoids On Chondrocyte mentioning

confidence: 99%

Articular cartilage destruction in experimental inflammatory arthritis: insulin-like growth factor-1 regulation of proteoglycan metabolism in chrondrocytes

et al. 1996

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Rheumatoid arthritis, a disease of unknown aetiology, is characterized by joint inflammation and, in its later stages, cartilage destruction. Inflammatory mediators may exert not only suppression of matrix synthesis but also cartilage degradation, which eventually leads to severe cartilage depletion. Systemically and locally produced growth factors and hormones regulate cartilage metabolism. Alterations in levels of these factors or in their activity can influence the pathogenesis of articular cartilage destruction in arthritic joints. The main topic of the present review is the role of the anabolic factor insulin-like growth factor-1 in the regulation of chondrocyte metabolic functions in normal and in diseased cartilage. This is the most important growth factor that balances chondrocytes proteoglycan synthesis and catabolism to maintain a functional cartilage matrix. A brief overview of how chondrocytes keep the cartilage matrix intact, and how catabolic and anabolic factors are thought to be involved in pathological cartilage destruction precedes the review of the role of this growth factor in proteoglycan metabolism in cartilage.

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“…Others still use terms related to development, such as "embryonic" (Folke and Stallard, 1967), "undifferentiated mesenchyme" (Oberg et al, 1967 (above); Oberg and Carlsson, 19791, "progenitor" (Silbermann and Maor, 1985), "germinal" (Silva and Hart, 19671, "prechondroblastic" (Carlson et a]., 1978), or "chondroblastic" (Carlson et a]., 1978;Stutzmann and Petrovic, 1979;Silbermann and Maor, 19851. Moreover, the demarcation between layers varies in different studies and is often imurecise (Silva and Hart, 1967: Stockli and Willert, 1971: Wright and Moffett, 1974Carlson et al, 1978;Silbermann and Maor, 1985;Ghafari and Degroote, 1966;Poole and Rosenberg, 1987). …”

Section: Type II Collagen Lmmunostainingmentioning

confidence: 99%

Cellular stages in cartilage formation as revealed by morphometry, radioautography and type II collagen immunostaining of the mandibular condyle from weanling rats

1988

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The role played by cell addition, cell enlargement, and matrix deposition in the endochondral growth of the condyle was assessed in weanling rats by four approaches making use of the light microscope: morphometry, 3H-thymidine radioautography, 3H-proline radioautography, and immunostaining for the cartilage-specific type II collagen. From the articular surface down, the condyle may be divided into five layers made up of cells embedded in a matrix: 1) the articular layer composed of static cells in a matrix rich in fibers presumed to be of type I collagen, 2) the polymorphic cell layer including the progenitor cells from which arise the cells undergoing endochondral changes, 3) the flattened cell layer in which cells produce a precartilagenous matrix devoid of type II collagen while undergoing differentiation in two stages: a "chondroblast" stage and a short "flattened chondrocyte" stage when intracellular type II collagen elaboration begins, 4) the upper hypertrophic cell layer, in which cells are "typical chondrocytes" that enlarge at a rapid rate, actively produce type II collagen, and deposit it into a cartilagenous matrix, and 5) the lower hypertrophic cell layer, composed of chondrocytes at a stage of terminal enlargement while the cartilagenous matrix is adapting for mineralization. 3H-thymidine radioautographic results indicate that the turnover time of progenitor cells in the polymorphic cell layer is about 2.9 days. The time spent by cells at each stage of development is estimated to be 1.4 days as chondroblasts, 0.5 days as flattened chondrocytes, 2.3 days as the chondrocytes of the upper hypertrophic cell layer, and 1.1 days as those of the lower hypertrophic cell layer. Calculations referring to a 1 x 1-mm square-sided column extending from the articular surface to the zone of vascular invasion provide the daily rate of cell addition (0.0077 mm3), extracellular matrix deposition (0.0127 mm3), and cell enlargement (0.0302 mm3). Hence the respective contribution of the three factors to condyle growth is in a ratio of about 1:1.6:4. This result emphasizes the role played by cell enlargement in the overall growth of the condyle.

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Receptor-mediated glucocorticoid inhibition of cell proliferation in mouse growth cartilage in vitro

Abstract: The growth hormone of neonatal facial cartilage from ICR mice is inhibited by glucocorticoid treatment in vitro. A reduction of the overall tissue weight is accompanied by a substantial decrease in the protein content of the tissue. For the first 48 h in culture,

Cited by 18 publications

References 10 publications

Effects of Dexamethasone and Vitamin D₃on Cartilage Differentiation in a Clonal Chondrogenic Cell Population

Effects of Dexamethasone and Vitamin D₃on Cartilage Differentiation in a Clonal Chondrogenic Cell Population

Articular cartilage destruction in experimental inflammatory arthritis: insulin-like growth factor-1 regulation of proteoglycan metabolism in chrondrocytes

Cellular stages in cartilage formation as revealed by morphometry, radioautography and type II collagen immunostaining of the mandibular condyle from weanling rats

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Receptor-mediated glucocorticoid inhibition of cell proliferation in mouse growth cartilage in vitro

Abstract: The growth hormone of neonatal facial cartilage from ICR mice is inhibited by glucocorticoid treatment in vitro. A reduction of the overall tissue weight is accompanied by a substantial decrease in the protein content of the tissue. For the first 48 h in culture,

Cited by 18 publications

References 10 publications

Effects of Dexamethasone and Vitamin D3on Cartilage Differentiation in a Clonal Chondrogenic Cell Population

Effects of Dexamethasone and Vitamin D3on Cartilage Differentiation in a Clonal Chondrogenic Cell Population

Articular cartilage destruction in experimental inflammatory arthritis: insulin-like growth factor-1 regulation of proteoglycan metabolism in chrondrocytes

Cellular stages in cartilage formation as revealed by morphometry, radioautography and type II collagen immunostaining of the mandibular condyle from weanling rats

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Effects of Dexamethasone and Vitamin D₃on Cartilage Differentiation in a Clonal Chondrogenic Cell Population

Effects of Dexamethasone and Vitamin D₃on Cartilage Differentiation in a Clonal Chondrogenic Cell Population