The role of Siglec-9/ Siglec-E in osteoclastogenesis

• Applicant: Dr. Ulrike Steffen
• Subject Area: Rheumatology
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 332396515

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are transmembrane receptors that recognize sialic acid-containing structures in glycoproteins and glycolipids. Siglec-9 and its murine homologue Siglec-E belong to the CD33-related Siglec subgroup and are mainly expressed on myeloid cells. Several studies have shown Siglec-9/ Siglec-E to influence migration and cytokine release of neutrophil granulocytes and macrophages. Bone resorbing osteoclasts are giant, multinucleated cells that develop by the fusion of macrophage-like precursor cells. Whether they are also affected by Siglec-9/ Siglec-E is not known so far. Our preliminary in vitro data strongly suggest Siglec-9/ Siglec-E to increase osteoclastogenesis. In addition, the injection of antibodies directed against Siglec-E attenuated inflammation and bone destruction in a murine serum-transfer arthritis model.The goal of the proposed project is to determine the role of Siglec-9/ Siglec-E in osteoclastogenesis under homeostatic and inflammatory conditions and to investigate, whether Siglec-9/ Siglec-E might be a suitable target for the treatment of inflammatory bone loss in diseases like rheumatoid arthritis. For this purpose, we will characterize the bone phenotype of Siglec-E deficient mice under homeostatic conditions, in two non-inflammatory osteoporosis models and in two arthritis models. In addition, we will investigate the mechanisms, by which Siglec-9/ Siglec-E influences osteoclastogenesis and determine the expression pattern of Siglec-9 in the joints of patients with rheumatoid arthritis.

• DFG Programme: Research Grants