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Novel Receptor:Ligand Interactions in Osteolytic Diseases

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Dissecting mechanisms of bone breakdown in disease

Advancing our knowledge of the process of bone development will improve treatment success of various autoimmune diseases involving pathological bone resorption. A European initiative provided significant insight into the mechanisms underlying bone breakdown by the specialised cells known as osteoclasts.

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The pathology of many osteolytic diseases such as osteoporosis and rheumatoid arthritis (RA) are linked with osteoclast-driven bone breakdown. This process of bone resorption results in the release of mineralised bone matrix and calcium into the bloodstream. Researchers in the field believe that the answer to the aberrant process of osteolysis lies in an understanding of the mechanisms involved in osteoclast development. To this end, the EU-funded project ‘Novel receptor: Ligand interactions in osteolytic diseases’ (NRLIOD) was designed to identify osteoclastogenic signals operating in osteolytic diseases, with particular emphasis on the receptors and ligands regulating osteoclast development. Prior work had identified the osteoclast associated receptor (OSCAR) to be involved in the process through binding to collagen structural proteins at sites of diseased joints. During the NRLIOD study, scientists generated a mouse knockout for OSCAR and analysed the bone phenotype. Additionally, they investigated the function of the receptor in a mouse model for arthritis that exhibits great disease penetrance. Results revealed a novel pathway of osteoclastogenesis to be associated with post-menopausal osteoporosis and to be up-regulated in RA. A new OSCAR ligand, the so-called Surfactant protein D (SP-D) was identified to confer a protective role in RA. NRLIOD work did not only shed light on the process of osteoclast development but also led to the discovery that OSCAR signalling in osteoclasts is involved in diseases such as osteoporosis. Project results have the potential to lead to the development of novel therapeutic reagents that suppress inflammation in lung disease and RA.

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