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Extracellular matrix changes in knee joint cartilage following bone-active drug treatment
Horst Claassen1, Christian Cellarius, Katharina E Scholz-Ahrens
1Institut für Anatomie und Zellbiologie der Martin-Luther-Universität Halle-Wittenberg, Grosse Steinstrasse 52, 06097, Halle, Germany. horst.claassen@medizin.uni-halle.de
Abstract:
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.
Insights
Certain medical treatments can harm articular cartilage, the tissue in joints. This study found that estrogen deficiency and long-term glucocorticoid use, especially with sodium fluoride, significantly reduce cartilage elasticity and content.
Area of Science:
- Biochemistry
- Orthopedics
- Pharmacology
Background:
- Certain medications and hormonal changes can negatively impact bone and cartilage health.
- Articular cartilage relies on its extracellular matrix, particularly glycosaminoglycans (GAGs), for elasticity and function.
- Understanding these effects is crucial for managing joint health during treatments affecting bone integrity.
Purpose of the Study:
- To investigate the detrimental effects of vitamin D/calcium deficiency, estrogen deficiency, and hypercortisolism on articular cartilage.
- To evaluate the combined impact of these conditions with bisphosphonates or sodium fluoride.
- To analyze changes in glycosaminoglycans (GAGs) and alkaline phosphatase (AP) activity in articular cartilage.
Main Methods:
- Utilized a Göttingen miniature pig model (n=29) to study articular cartilage from knee joints.
- Quantified glycosaminoglycan (GAG) content using a spectrometric method with dimethylene blue chloride.
- Localized alkaline phosphatase (AP) activity via enzyme histochemistry and counted positive chondrocytes, alongside histochemical staining for sulfated GAGs.
Main Results:
- Ovariectomized and long-term glucocorticoid-treated pigs showed a significant decrease in GAG content compared to controls.
- The glucocorticoid/sodium fluoride group exhibited significantly diminished GAGs and fewer AP-positive chondrocytes.
- Short-term glucocorticoid treatment resulted in slightly higher GAG content and more AP-positive chondrocytes than controls.
Conclusions:
- Estrogen deficiency and long-term glucocorticoid therapy negatively affect articular cartilage extracellular matrix composition and elasticity.
- Combination therapy with sodium fluoride exacerbates these detrimental effects.
- These findings highlight potential risks to joint health associated with specific medical treatments.
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