Siglec-15 on osteoclasts is crucial for bone erosion in serum-Transfer arthritis

Korn M, Schmitt H, Angermüller S, Chambers D, Seeling M, Lux U, Brey S, Royzman D, Bruckner C, Popp V, Percivalle E, Bäuerle T, Zinser E, Winkler T, Steinkasserer A, Nimmerjahn F, Nitschke L (2020)

Publication Type: Journal article

Publication year: 2020


Book Volume: 205

Pages Range: 2595-2605

Journal Issue: 10

DOI: 10.4049/jimmunol.2000472


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-152/2 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.

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Korn, M., Schmitt, H., Angermüller, S., Chambers, D., Seeling, M., Lux, U.,... Nitschke, L. (2020). Siglec-15 on osteoclasts is crucial for bone erosion in serum-Transfer arthritis. Journal of Immunology, 205(10), 2595-2605.


Korn, Marina, et al. "Siglec-15 on osteoclasts is crucial for bone erosion in serum-Transfer arthritis." Journal of Immunology 205.10 (2020): 2595-2605.

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