Project X

Modulation of formation and activity of different subsets of osteoclasts by anti-resorptive compounds, focus on assay development.

Giuliana Ascone

I am Giuliana Ascone and I am from Italy and particularly from Caltagirone, a small town in province of Catania – Sicily. I did my studies at the University of Parma, where I got first my  Bachelor degree in Biotechnology and then the Master Degree in Medical Biotechnology.

During the master internship I worked on the differentiation of Placental Mesenchymal Stem Cells (pMSCs), exploring their potency in chondrogenic differentiation compared to adult chondrocytes in order to provide more suitable approaches for cartilage repair and regeneration.

Since April 2014 I joined the EUROCLAST Consortium and I am working as an Early Stage  Researcher (ESR) Future Diagnostic, Wijchen in The Netherlands.  Much of my experimental work is performed at the Department of Experimental Rheumatology, embedded in the Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen -   The Netherlands.

When I am not busy with my research I like dedicate myself to my hobbies, which are singing, photography and walking and spending  time with friends. You can contact me via e-mail at Giuliana.ascone@radboudumc.nl

Ernst Lindhout

My name is Ernst Lindhout, I am educated as biochemist and have a PhD in Immunology. I have been working at Future Diagnostics for more than 13 years. I started as research scientist and since May 2012 I am Director of Research and Development.

Our expertise encompasses a wide array of disease areas and detection technologies, aimed to develop regulatory-grade in vitro diagnostic (IVD) assays. I have developed a large number of manual and automated immunoassays with a broad variety of antigens from hormones to infectious disease assays.

We also developed several immunoassays for metabolic bone diseases (i.e. PTH, Calcitonin and 25-OH Vitamin D). Since metabolic bone diseases are receiving more attention, we are very interested in expanding our knowledge of assays for these diseases. Future Diagnostics is partner in several European Consortia as SME where we use our knowledge and experience to get a newly discovered biomarker developed into an assay for the IVD market.

Outside my work I enjoy nosing and tasting of single malt scotch whisky, and visiting (rock) concerts and art exhibitions. I can be reached via e-mail at Lindhout.e@future-diagnostics.nl

Peter van Lent

My name is Peter van Lent and my research interest is to get a better understanding of the mechanisms involved in the interaction between the innate immune system and joint pathology with respect to cartilage and bone destruction in rheumatic diseases. Focus thereby lies on macrophages and their mediators.

I am located at the Radboud Institute for Molecular Life Sciences where my research team is embedded in the Radboud theme “Inflammatory diseases”. By working together with scientists, technicians and clinicians we hope to translate our findings in basic research to develop new diagnostics and therapeutic tools in inflammation like i.e. stem cell therapy. We participate in several European networks which aim to develop new diagnostic and therapeutic approaches to be translated into the clinic.

When I am not at work I like to spend my free time in gardening and meditating. Beyond that, my hobbies are walking and biking which allow me to enjoy the beauty of nature. You can contact me via e-mail on Peter.vanlent@radboudumc.nl


Our Project

This project within EUROCLAST aims to develop a bone resorption assay for high-throughput screenings based on ERHoxb8 cells, a myeloid precursor-derived cell line.  

This cell line will be transfected with a lentiviral construct where luciferase is under the control of the Cathepsin K (CtsK) promoter, to mimic its high level expression in active osteoclasts. This will enable us to set up a disease-responsive assay that relies on the amplification of the signal when osteoclasts are activated. Various anti-resorptive compounds will then be tested for their ability to inhibit osteoclast formation and activity.

Using this cell line we also propose to identify novel mediators involved in bone destruction  and perform mechanistic studies to understand how bone resorption can be inhibited.

Therefore, in another part of the project, we are investigating the role of apolipoprotein E (ApoE), which in addition to its anti-inflammatory properties has also been shown to play a role in modulating bone metabolism. We will focus on the ability of ApoE to inhibit osteoclast activity.

To better understand the contribution of ApoE in bone destruction, in vivo experiments will be performed in Apo E deficient mice and the mechanisms of action will be further investigated  in vitro.

Our postal address is:
Radboud University Medical Center
272, Experimental Rheumatology
PO Box 9101
6500 HB Nijmegen
The Netherlands

Giuliana Ascone with her supervisors

Here I am with my supervisors: from left to right: Ernst, me Giuliana, and Peter.