Cited by 46Bone Metabolism and DiseasesGlycosylation and Glycoproteins ResearchPhagocytosis and Immune Regulation

Sialylation of TLR2 initiates osteoclast fusion

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Dou, Ce, Zhen, Gehua, Dan, Yang, Wan, Mei, Limjunyawong, Nathachit, Cao, Xu·2022·Bone Research

Abstract

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 ST3Gal1. Interestingly, the expression of Siglec15 in macrophages was activated by M-CSF, whereas ST3Gal1 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.

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Authors
Dou, C., Zhen, G., Dan, Y., Wan, M., Limjunyawong, N., & Cao, X.
Affiliations
Johns Hopkins University (US)
Corresponding author
Cao, Xu
Venue
Bone Research
Published
2022-03-02
Volume
10
Issue
1
Pages
24-24
ISSN
  • 2095-4700 (ISSN-L)
  • 2095-6231
OpenAlex
W4214826194
Cited by
46
References
59
Citations by year
2026: 15 · 2025: 10 · 2024: 10 · 2023: 11
FWCI
2.53
Type
journal article
Language
en
Open access
Locations
  • Bone Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Johns Hopkins University
  • National Institutes of Health
  • National Institute on Aging (RF1AG068997, P01AG066603, R01AG076783)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR071432)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
osteoclastogenesis, osteoclast fusion, Siglec-15, sialic acid, ST3GAL1, sialyltransferase, RANKL, macrophage colony-stimulating factor, macrophages, cell recognition, bone resorption, bone formation

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