P. Kraan Van Der (Nijmegen, NL)

Radboud University Nijmegen Rheumatology
Peter van der Kraan is professor of Experimental Rheumatology and has over 30 years of experience investigating the changing role of growth factor signaling in rheumatic diseases. Research areas includes the pathobiology of osteoarthritis (OA) with a special interest in the role of growth factors and cytokines (e.g. TGF beta; BMPs; GDFs; Wnts) and their intracellular signaling pathways in pathological processes. Research is focused on the elucidation of the mechanism of tissue destruction and application of this knowledge in the prevention of tissue damage and the stimulation of tissue regeneration. To elucidate the pathological mechanisms; Prof van der Kraan’s group uses in vitro cell culture systems; viral over expression systems both in vitro and in vivo; tissue specific; inducible murine mouse models; sophisticated experimental models of tissue damage; repair; fibrosis and human tissues. His group was the first to identify the role of TGF β in the pathophysiology of osteoarthritis demonstrating that TGF β plays a protective role in young healthy joints and has a deleterious role in aged and osteoarthritic joints. In chondrocyte differentiation the role of TGF beta superfamily signaling in chondrocyte terminal differentiation has been and is still under study.

Presenter Of 1 Presentation

Poster Stem Cells

P225 - Transcription factor reporters suitable for monitoring patient dependent chondrogenic capacity in osteoarthritis

Presentation Topic
Stem Cells
Date
13.04.2022
Lecture Time
09:30 - 09:30
Room
Exhibition Foyer
Session Name
7.3 - Poster Viewing / Coffee Break / Exhibition
Session Type
Poster Session
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Recent developments have demonstrated that intrinsic cartilage repair is possible in certain osteoarthritis (OA) patients. Literature suggests an influence of joint microenvironment on intrinsic cartilage repair via affecting chondrogenic capacity of stem cells. A method able to discriminate between patients with permissive or non-permissive articular joint microenvironments would be of great use to predict the outcome of cartilage repair therapies. Therefore, our goal is to develop a rapid bioassay that will be able to discriminate between these joint conditions.

Methods and Materials

To construct our bioassay, sixteen transcription factor binding sequences were cloned in the pNL1.2 vector. Transcription factor reporter constructs were stably integrated into SW1353 cells using virus transduction. Cells were stimulated for 6 hours with OA-synovium conditioned medium (OAs-cm; n=32) and luciferase activity was measured. These results were correlated (Pearson) with the ability of these OAs-cm to inhibit sGAG formation during chondrogenesis. This was tested by chondrogenic differentiation of human fetal bone-marrow derived MSCs in an established three-dimensional pellet culture model. Pellets were cultured for 14 days in chondrogenic medium and were exposed to OAs-cm after 10 days of differentiation. Cartilage formation was determined at day 14 by measuring sGAG content.

Results

Large heterogeneity was observed in the response of the transcription factor reporters between the OAs-cm from individual patients. Furthermore, individual OAs-cm reduced sGAG content of differentiating MSCs by a range between 3% and 65%. Significant correlations were found between the fold change of the reporter activity and the percentage of inhibition on chondrogenesis for seven out of the sixteen tested transcription factor reporters (AP1, CRE, ISRE, NFAT5, NFκB, SIE and SRE; Figure 1).

abstract figure 1.png

Conclusion

This set of seven transcription factor reporters appears to be able to predict repair capacity of stem cells in an OA microenvironment and could be of use for a personalized treatment strategy.

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Meeting Participant Of

Tegel Meeting Room (50) ICRS Committee Meeting