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

Abstract

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 2/2 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.

Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients

“…The animal procedures have been approved by the “Regierung of Unterfranken” and were conducted in accordance with the guidelines of the Federation of European Laboratory Animal Science Associations (FELASA; Approval numbers: 55.2-DMS-2532-2-114 from 13 November 2015 and 10 December 2015; TS-3/14 from 21 February 2014). Pooled serum from transgenic K/BxN mice ( 29 , 38 ) was kindly provided by F.Nimmerjahn. 200µl serum was injected intraperitoneally into 10 week old female C57Bl/6 mice (Janvier, Le Genest-Saint-Isle, France).…”

“…200µl serum was injected intraperitoneally into 10 week old female C57Bl/6 mice (Janvier, Le Genest-Saint-Isle, France). Arthritis scoring was carried out in a blinded manner with a score system ranging from 0 (no swelling) to 3 (massive swelling) as described previously ( 38 ).…”

“…The outcome in the present study was measured by quantifying the subjective pain reduction in terms of percentage of improvement with reference to their initial pain status before LDRT. The interrogation of patients was performed directly after the last radiotherapy session and during the follow-up appointments 8 to Arthritis scoring was carried out in a blinded manner with a score system ranging from 0 (no swelling) to 3 (massive swelling) as described previously (38).…”

“…K/BxN Mouse Model and Arthritis Scoring BxN mice(29,38) was kindly provided by F.Nimmerjahn. 200µl serum was injected intraperitoneally into 10 week old female C57Bl/6 mice (Janvier, Le Genest-Saint-Isle, France).…”

Radon Improves Clinical Response in an Animal Model of Rheumatoid Arthritis Accompanied by Increased Numbers of Peripheral Blood B Cells and Interleukin-5 Concentration

“…These effects are also visualized in (H), where the ∆ clinical score [d7-d10] of clinical progression is significantly better in radon treated animals when compared to mock controls. Arthritis score evaluation was carried out in a blinded manner with a score system ranging from 0 (no swelling) to 3 (massive swelling) as described previously [31]. The experimental set-up for in vivo radon exposure can be seen in Figure 1C,D.…”