Investigating Ror2-dependent non-canonical Wnt signaling in bone remodeling

Project Information

ROR2BONE

Grant agreement ID: 658632

DOI

10.3030/658632

Project terminated on 31 December 2017

EC signature date 2 April 2015

Start date 1 May 2015

End date 2 November 2018

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 171 460,80

EU contribution

€ 171 460,80

Coordinated by

UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF
Germany

Periodic Reporting for period 1 - ROR2BONE (Investigating Ror2-dependent non-canonical Wnt signaling in bone remodeling)

Reporting period: 2015-05-01 to 2017-04-30

Summary of the context and overall objectives of the project

Osteoporosis is a very common disease in aging societies, leading to a decrease in bone mass and strength and ultimately fragility fractures. Fragility fractures cause pain and an immobilization and lead to an increased morbidity and mortality. Thus, osteoporosis has a great socio-economic impact that is very likely to increase as populations age. Bones are constantly dismantled and rebuild by bone-resorbing osteoclasts and bone-forming osteoblasts. Thus, current specific osteoporosis therapies are focusing on decreasing bone resorption or on increasing bone formation. However, the drugs that are available thus far have side effects, might not be applicable due to concomitant diseases or can only be administered for a limited period of time. It is therefore important to better understand the molecular and cellular processes by which the bone tissue is formed and resorbed, to identify novel targets that could facilitate the development of future therapies. This project is focusing on exploring novel regulatory circuits of the Wnt pathway, which is known to be a strong inducer of bone formation.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In this project we focused on investigating the function of the Ror2 on bone turnover. We uncovered that this receptor regulates osteoblast differentiation and function and controls bone mass. This effect was mediated in a cell-autonomous manner and the findings were confirmed in vitro and in vivo. Next, we performed an unbiased screen to obtain information regarding the underlying molecular mechanisms. This screen revealed strong candidate genes and our ongoing experiments are aimed at further elucidating the molecular mechanisms by which the receptor affects bone remodeling. In a next step, we intend to investigate this mechanism in the context of a novel anti-osteopororsis therapy.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This project provides novel insights on the regulation of bone metabolism. This knowledge might help to identify new candidate targets that could be used to develop future therapies to treat conditions of bone fragility. This could improve the cure of osteoporosis as a debilitating disease and therefore have a great societal impact.

Scheme of the domains of Ror2