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Korn, Marina A.; Schmitt, Heike; Angermüller, Sieglinde; Chambers, David; Seeling, Michaela; Lux, Uwe T.; Brey, Stefanie; Royzman, Dmytro; Brückner, Christin; Popp, Vanessa; Percivalle, Elena; Bäuerle, Tobias; Zinser, Elisabeth; Winkler, Thomas H.; Steinkasserer, Alexander; Nimmerjahn, Falk; Nitschke, Lars

Siglec-15 on Osteoclasts Is Crucial for Bone Erosion in Serum-Transfer Arthritis

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  • Media type: E-Article
  • Title: Siglec-15 on Osteoclasts Is Crucial for Bone Erosion in Serum-Transfer Arthritis
  • Contributor: Korn, Marina A.; Schmitt, Heike; Angermüller, Sieglinde; Chambers, David; Seeling, Michaela; Lux, Uwe T.; Brey, Stefanie; Royzman, Dmytro; Brückner, Christin; Popp, Vanessa; Percivalle, Elena; Bäuerle, Tobias; Zinser, Elisabeth; Winkler, Thomas H.; Steinkasserer, Alexander; Nimmerjahn, Falk; Nitschke, Lars
  • imprint: The American Association of Immunologists, 2020
  • Published in: The Journal of Immunology
  • Language: English
  • DOI: 10.4049/jimmunol.2000472
  • ISSN: 0022-1767; 1550-6606
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
  • Access State: Open Access