J. Ekholm (Gothenburg, SE)

Institute of Biomedicine at Sahlgrenska Academy Department of Clinical Chemistry and Transfusion Medicine

Presenter Of 1 Presentation

Podium Presentation Osteoarthritis

16.3.9 - Vitamin D3 inhibits ADAMTS-4 and MMP13

Presentation Number
16.3.9
Presentation Topic
Osteoarthritis
Lecture Time
12:27 - 12:36
Session Type
Free Paper Session
Corresponding Author
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

OA develops because it is an imbalance between catabolic and anabolic processes resulting in gradual degradation of cartilage. Inflammation and mechanical strain are the causes of increased degradation. It is therefore of utmost importance to find a drug or a natural molecular substance that can stop catabolic processes. Several studies have suggested a link between vitaminD status and OA; some have found that individuals deficient in vitaminD have an increased risk of progressive knee-osteoarthritis, and there are reports of a pain reducing effect of oral supplementation. Of importance, vitaminD has been suggested to dampen inflammation-driven diseases such as OA. VitaminD has been detected in the synovial fluid and chondrocytes express the vitaminD receptor. The aim of this study was to investigate if the vitaminD affects the expression of some of the regulatory proteins that regulate cartilage catabolism, focusing on the metabolism of Aggrecan and Collagen2.

Methods and Materials

Cells, taken from patients with secondary OA, were cultured in monolayer and treated with vitaminD. Half of the cells were also treated with IL1B to mimic an inflammatory condition. The expression of GDF5, ADAMTS-4 and MMP-13 were analyzed with qPCR. The cell medium was collected and ELISA was performed to quantify the amount of the Aggrecan neoepitope ARGS, generated from ADAMTS-4-mediated cleavage of Aggrecan.

Results

VitaminD downregulated the expression of ADAMTS-4, MMP-13, both in the absence and presence of IL1β. IL1β itself had a significant stimulating effect on the expression of these genes. Furthermore, vitaminD upregulated the expression of TIMPs, as well as GDF5, a protein known to stimulate anabolic processes. Quantification of neoepitopes of Aggrecan is still performed.

Conclusion

VitaminD prevents degradation of Collagen and Aggrecan by downregulating the Aggrecan-specific proteinase ADAMTS-4 and Collagen-specific proteinase MMP-13 and also, by upregulating TIMP-1, TIMP-2 and TIMP-3, inhibitors of ADAMTs and MMPs.

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