Journal
BONE
Volume 143, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2020.115665
Keywords
Osteoclasts; Siglec-E; Siglec-9; Bone; Resorption
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [HA 8163/1-1, FOR2886PANDORA -TP4, SFB1181]
- Bundesministerium fur Bildung und Forschung (BMBF
- METARTHROS)
- Staedtler Stiftung (WW/eh 20/17)
- European Union (ERC Synergy grant) [810316]
- EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking RTCure grant [777357]
- ELAN Fond of the Friedrich-Alexander-Universitat Erlangen-Nurnberg [15-08-17-1]
- European Research Council (ERC) [810316] Funding Source: European Research Council (ERC)
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Siglec-9 and Siglec-E are inhibitory receptors expressed at all stages of osteoclastogenesis in humans and mice, suppressing osteoclast function independently of differentiation. Knockout of Siglec-E in mice resulted in lower bone mass despite unchanged osteoclast numbers and increased bone formation rate.
Regulation of osteoclast differentiation and function is a central element in bone homeostasis. While the role of soluble factors, such as cytokines, hormones and growth factors, in controlling osteoclast differentiation has been intensively characterized, the function of surface receptors is less well understood. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9 and its murine homolog Siglec-E are sialic acid-recognizing inhibitory receptors from the CD33-related Siglec-family and mainly expressed on myeloid cells. We found Siglec-9 and Siglec-E to be expressed at all stages of human and murine osteoclastogenesis, respectively. Siglec-E knockout mice displayed lower bone mass despite unchanged osteoclast numbers and an increased bone formation rate. Ex vivo osteoclast assays using Siglec-E knockout cells or a blocking antibody against human Siglec-9 confirmed the suppressive effect of Siglec-9/Siglec-E on osteoclast function. Although osteoclast numbers were unchanged or even slightly decreased, the blockade/absence of Siglec-9/Siglec-E resulted in an augmented resorption activity of mature osteoclasts. This increased resorption activity was associated with enlarged actin rings. Together, our results suggest Siglec-9/Siglec-E to inhibit osteoclast activation independently from osteoclast differentiation and thereby propose a new mechanism for the control of local bone resorption.
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