Siglec-15 on Osteoclasts Is Crucial for Bone Erosion in Serum-Transfer Arthritis
| Autor: | Thomas Winkler, Elena Percivalle, Dmytro Royzman, Falk Nimmerjahn, Vanessa Popp, Alexander Steinkasserer, Marina A Korn, Stefanie Brey, Elisabeth Zinser, Lars Nitschke, Michaela Seeling, Heike Schmitt, David Chambers, Sieglinde Angermüller, Uwe Thorsten Lux, Tobias Bäuerle, Christin Brückner |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Cell type Primary Cell Culture Immunology Pathologic bone resorption Immunoglobulins Osteoclasts Arthritis Inflammation Biology Bone and Bones Arthritis Rheumatoid Mice 03 medical and health sciences 0302 clinical medicine Immune system Osteoclast medicine Animals Humans Immunology and Allergy Bone Resorption Cells Cultured Mice Knockout Membrane Proteins SIGLEC respiratory system medicine.disease Arthritis Experimental medicine.anatomical_structure Knockout mouse Leukocytes Mononuclear Cancer research Female medicine.symptom 030215 immunology |
| Zdroj: | The Journal of Immunology. 205:2595-2605 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2000472 |
| Popis: | Siglec-15 is a conserved sialic acid–binding Ig-like lectin, which is expressed on osteoclasts. Deficiency of Siglec-15 leads to an impaired osteoclast development, resulting in a mild osteopetrotic phenotype. The role of Siglec-15 in arthritis is still largely unclear. To address this, we generated Siglec-15 knockout mice and analyzed them in a mouse arthritis model. We could show that Siglec-15 is directly involved in pathologic bone erosion in the K/BxN serum-transfer arthritis model. Histological analyses of joint destruction provided evidence for a significant reduction in bone erosion area and osteoclast numbers in Siglec-15−/− mice, whereas the inflammation area and cartilage destruction was comparable to wild-type mice. Thus, Siglec-15 on osteoclasts has a crucial function for bone erosion during arthritis. In addition, we generated a new monoclonal anti–Siglec-15 Ab to clarify its expression pattern on immune cells. Whereas this Ab demonstrated an almost exclusive Siglec-15 expression on murine osteoclasts and hardly any other expression on various other immune cell types, human Siglec-15 was more broadly expressed on human myeloid cells, including human osteoclasts. Taken together, our findings show a role of Siglec-15 as a regulator of pathologic bone resorption in arthritis and highlight its potential as a target for future therapies, as Siglec-15 blocking Abs are available. |
| Databáze: | OpenAIRE |
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