| First Author | Korn MA | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 10 | Pages | 2595-2605 |
| PubMed ID | 33020147 | Mgi Jnum | J:304061 |
| Mgi Id | MGI:6502498 | Doi | 10.4049/jimmunol.2000472 |
| Citation | Korn MA, et al. (2020) Siglec-15 on Osteoclasts Is Crucial for Bone Erosion in Serum-Transfer Arthritis. J Immunol 205(10):2595-2605 |
| abstractText | 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. |
