Siglec-15 as a potential molecule involved in osteoclast differentiation and bone metabolism

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is a well-conserved type I transmembrane protein of the Siglecs family, distributed in macrophages and dendritic cells in the human spleen and lymph nodes. As an immune receptor, Siglec-15 is expressed in almost all branches of the spinal cord. Siglec-15 participates in the metabolism of the skeleton by regulating osteoclast activity and differentiation and has an influential role in dynamic bone remodelling. The binding of DNAX activation protein of 12 kDa (DAP12), which contains the immunoreceptor tyrosine-based activation motif (ITAM) activation domain, to the Siglec-15 receptor provides a positive stimulatory signal for osteoclast growth, with the involvement of the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) signalling. Recently, Siglec-15 antibodies have been shown to effectively prevent bone resorption in mouse models of osteoporosis and accelerate fracture healing to some extent. Therefore, exploring the molecular characteristics and functions of Siglec-15 may lead to new therapeutic strategies for common clinical skeletal diseases.