Sialylation of TLR2 initiates osteoclast fusion  

作　　者：Ce Dou Gehua Zhen Yang Dan Mei Wan Nathachit Limjunyawong Xu Cao 

机构地区：[1]Department of Orthopedic Surgery,Institute of Cell Engineering and Department of Biomedical Engineering,Johns Hopkins University School of Medicine,Baltimore,MD,USA [2]The Solomon H.Snyder Department of Neuroscience,Johns Hopkins University School of Medicine,Baltimore,MD,USA

出　　处：《Bone Research》2022年第2期286-296,共11页骨研究（英文版）

基　　金：supported by US National Institutes of Health grants AR 071432 (to X.C.)

摘　　要：The molecular control of osteoclast formation is still not clearly elucidated. Here, we show that a process of cell recognition mediated by Siglec15-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 Siglec15 has not been identified, and the signaling mechanism involving Siglec15 in osteoclast function remains unclear. We found that Siglec15 bound sialylated TLR2 as its receptor and that the binding of sialylated TLR2 to Siglec15 in macrophages committed to the osteoclast-lineage initiated cell fusion for osteoclast formation, in which sialic acid was transferred by the sialyltransferase ST3 Gal1. Interestingly, the expression of Siglec15 in macrophages was activated by M-CSF, whereas ST3 Gal1 expression was induced by RANKL. Both Siglec15-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 Siglec15 initiates cell fusion for osteoclast formation.

关 键 词：OSTEOCLAST TLR2 INJECTION 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]