摘要The molecular control of osteoclast formation is still not clearly elucidated.Here,we show that a process of cell recognition mediated by Siglec1 5-TLR2 binding is indispensable and occurs prior to cell fusion in RANKL-mediated osteoclastogenesis.Siglec15 has been shown to regulate osteoclastic bone resorption.However,the receptor for Siglec1 5 has not been identified,and the signaling mechanism involving Siglec1 5 in osteoclast function remains unclear.We found that Siglec1 5 bound sialylated TLR2 as its receptor and that the binding of sialylated TLR2 to Siglec1 5 in macrophages committed to the osteoclast-lineage initiated cell fusion for osteoclast formation,in which sialic acid was transferred by the sialyltransferase ST3Gal1.Interestingly,the expression of Siglec1 5 in macrophages was activated by M-CSF,whereas ST3Gal1 expression was induced by RANKL.Both Siglec1 5-specific deletion in macrophages and intrafemoral injection of sialidase abrogated cell recognition and reduced subsequent cell fusion for the formation of osteoclasts,resulting in increased bone formation in mice.Thus,our results reveal that cell recognition mediated by the binding of sialylated TLR2 to Siglec1 5 initiates cell fusion for osteoclast formation.