Physiological levels of hydrocortisone maintain an optimal chondrocyte extracellular matrix metabolism

Wang, Jun; Elewaut, Dirk; Hoffman, Ilse; Veys, Eric; Verbruggen, G.

doi:10.1136/ard.2002.005298

Cited by 16 publications

(11 citation statements)

References 44 publications

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“…The influence of glucocorticoids on the synthesis of PG and GAG is controversial. In cultivated human articular chondrocytes, physiological doses of hydrocortisone are reported to lead to a decreased catabolic signaling pathway (Wang et al 2004) or to an elevated synthesis (Almqvist et al 2000) of aggrecan as the large PG of articular cartilage. A decrease in cell organelles, such as the Golgi apparatus or endoplasmic reticulum, and a reduction in the size of mitochondria have been observed in knee joint chondrocytes when rabbits are treated with 10 mg hydrocortisone per kilogram body weight for 36 days (Wassilev and Owtscharov 1972); since the effectiveness of hydrocortisone to prednisolone follows the proportion 1:4, these rabbits have received an equivalent dose five times higher than that given to our miniature pigs.…”

Section: Long-term Treatment With Glucocorticoidsmentioning

confidence: 99%

“…Following estrogen application, a decrease of type-II-collagen degradation products in urine has been observed in ovariectomized rats (Hoegh-Andersen et al 2004), whereas no significant effect on the collagen content of articular cartilage has been measured in ovariectomized cynomolgus monkeys (Ham et al 2004). Glucocorticoids are reported to increase or to decrease the synthesis of extracellular matrix components of articular cartilage depending on the species investigated or on the applied concentrations of the hormone (Almqvist et al 2000;Fubini et al 2001;Wang et al 2004;Doyle et al 2005). Recently, evidence has indicated that bisphosphonates might be chondroprotective in rabbits with chymopapain-induced articular cartilage damage (Mühlemann et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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Extracellular matrix changes in knee joint cartilage following bone-active drug treatment

et al. 2006

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Certain drugs or treatments that are known to affect bone quality or integrity might have side effects on the extracellular matrix of articular cartilage. We investigated the effects of vitamin D and calcium deficiency, estrogen deficiency, and hypercortisolism alone or in combination with bisphosphonates or sodium fluoride in an animal model, viz., the Göttingen miniature pig (n=29). The articular cartilage from knee joints was analyzed for its content of glycosaminoglycans (GAGs, as macromolecules responsible for the elasticity of articular cartilage) by a spectrometric method with dimethylene blue chloride. In cryo- or paraffin sections, alkaline phosphatase (AP, as an enzyme indicating mineralization or reorganization of articular cartilage matrix) was localized by enzyme histochemistry, and positive cells were counted, whereas differently sulfated GAGs were stained histochemically. A significant decrease in GAG content was measured in ovariectomized and long-term glucocorticoid-treated animals compared with untreated animals. In the glucocorticoid/sodium fluoride group, GAGs were significantly diminished, and significantly fewer AP-positive chondrocytes were counted compared with the control. GAG content was slightly higher, and significantly more AP-positive chondrocytes were counted in short-term glucocorticoid-treated animals then in the control group. GAGs, as part of proteoglycans, are responsible for the water-storage capacity that gives articular cartilage its unique property of elasticity. Thus, ovariectomy and long-term glucocorticoid therapy, especially when combined with sodium fluoride, have detrimental effects on this tissue.

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Section: Long-term Treatment With Glucocorticoidsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Extracellular matrix changes in knee joint cartilage following bone-active drug treatment

et al. 2006

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“…matrix metalloproteinase (MMP) and aggrecanase families (8,9), and subsequent replacement with new protein synthesized by chondrocytes (10,11), resulting in a balance between anabolism and catabolism. With the onset of OA, the balance shifts toward degradation.…”

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confidence: 99%

Global analyses of gene expression in early experimental osteoarthritis

Appleton¹,

Pitelka²,

Henry³

et al. 2007

Arthritis & Rheumatism

222

224

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Objective. To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis.Methods. OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery.Results. After normalization, comparison of OA and sham-operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression >1.5-fold, 722 with changes >2-fold, 135 with changes >4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control.Conclusion. Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation.

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“…the CM and FRM; this closely resembles the organization of joint cartilage. Chondrocytes in an alginate matrix have been previously used by several investigators to study the effect of a combination of physical and biochemical factors or a pair of parameters (such as the effect of hydrostatic pressure and growth factors) on cell metabolism and morphology (D'Souza et al 2000;Nerucci et al 2000;Sadowski and Steinmeyer 2002;van Osch et al 1998;Wang et al 2004). …”

Section: Discussionmentioning

confidence: 99%

Regeneration of static-load-degenerated articular cartilage extracellular matrix by vitamin C supplementation

2008

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The effect of a physiological dose of vitamin C (100 microg/ml) on goat articular cartilage chondrocytes cultured in an alginate matrix and subjected to static pressurization of 2.4 MPa was investigated. Biochemical analyses of DNA, glycosaminoglycan (GAG), collagen and protease activity were carried out in various matrix fractions, i.e. cellular matrix (CM) and further removed matrix (FRM), and in culture medium. The treatment of chondrocytes with vitamin C after static pressure increased the GAG content in both CM and FRM (P < 0.03) as compared with control or vitamin C/ static load alone. The collagen content of chondrocytes treated with vitamin C alone and vitamin C after static load also increased significantly in FRM (P < 0.003) as compared with control and static load alone. The specific activity of protease in CM and FRM decreased after vitamin C supplementation both with and without static pressure relative to control (P < 0.003). Transmission electron-microscopic images showed a mixed population of spherical and elliptical chondrocytes when vitamin C was added after static load as compared with static load alone where only elliptical cells were seen. Abundant pericellular and collagen fibrils were seen in this group of chondrocytes as compared with all other groups and the control. The results thus show that, in vitro, vitamin C supplementation of chondrocytes after static loading has the potential to reduce the morphological and biochemical degeneration of chondrocytes caused by static loading, thereby improving the cellular health and functioning of articular cartilage.

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Physiological levels of hydrocortisone maintain an optimal chondrocyte extracellular matrix metabolism

Cited by 16 publications

References 44 publications

Extracellular matrix changes in knee joint cartilage following bone-active drug treatment

Extracellular matrix changes in knee joint cartilage following bone-active drug treatment

Global analyses of gene expression in early experimental osteoarthritis

Regeneration of static-load-degenerated articular cartilage extracellular matrix by vitamin C supplementation

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