Siglec-15, a member of the sialic acid-binding lectin, is a novel regulator for osteoclast differentiation

Mechanism and Function of Monoclonal Antibodies Targeting Siglec-15 for Therapeutic Inhibition of Osteoclastic Bone Resorption

“…1A, by Western blotting, there was a dramatic increase in Siglec-15 protein in both the human and murine differentiated osteoclasts (see Fig. 1A, lanes 2 and 4), in agreement with previous RT-PCR experiments (3,5).…”

“…We examined the importance of Siglec-15 in tissue culture models of osteoclastogenesis and found that RNAi-mediated knockdown of Siglec-15 expression impaired RANKL-induced differentiation of primary human osteoclast precursors (HOPs) and the mouse RAW264.7 cell line (3). A recent study reported the overexpression of Siglec-15 in giant cell tumors of the bone, which are characterized by abundant osteoclast-like cells, and in agreement with our results, the authors observed dramatic up-regulation of Siglec-15 mRNA in differentiating HOPs and RAW264.7 cells (5). The effect of Siglec-15 RNAi on osteoclast differentiation has since been independently confirmed in mouse bone marrow macrophages (6).…”

Siglec-15 Protein Regulates Formation of Functional Osteoclasts in Concert with DNAX-activating Protein of 12 kDa (DAP12)

“…Hinuma et al (33) reported that anti-Siglec-15 antibody inhibited RANKL-and TNF-␣-induced osteoclast formation in vitro, not only in mouse but also in human cells. These results suggest the important role of the Siglec-15 extracellular domain in human cells as well.…”

Glucosamine Suppresses Osteoclast Differentiation through the Modulation of Glycosylation Including <i>O</i>-GlcNAcylation

“…13) In addition, sugar-binding proteins such as siglec, which interact with sialic acid, and galectins, which interact with Galβ1-4GlcNAc, also have important roles in osteoclastogenesis. [14][15][16][17][18][19] Therefore, in order to clarify the potential for GlcN-mediated glycosylation modification, we investigated the effect of GlcN treatment on the pattern of glycosylation using lectin blotting of cell extracts with SSA, MAM, RCA120, PHA-E 4 , Con A, and LCA, which mainly recognize α2,6-linked sialic acid, α2,3-linked sialic acid, Galβ1-4GlcNAc, bisecting GlcNAc, high mannose type Nglycan, and N-glycan core modified with fucose, respectively (Figs. 2B-G).…”