Roles of the Siglec family in bone and bone homeostasis

Tremendous progress has been seen in the study of the role of sialic acid binding im-munoglobulin type lectins (Siglecs) in osteoimmunology in the past two decades. Interest in Siglecs as immune checkpoints has grown from the recognition that Siglecs have relevance to human disease. Siglecs play important roles in inflammation and cancer, and play key roles in immune cell signaling. By recognizing common sialic acid containing glycans on glycoproteins and glycolipids as regulatory receptors for immune cell signals, Siglecs are expressed on most immune cells and play important roles in normal homeostasis and self-tolerance. In this review, we describe the role that the siglec family plays in bone and bone homeostasis, including the regulation of osteoclast differentiation as well as recent advances in inflammation, cancer and osteoporosis. Particular emphasis is placed on the relevant functions of Siglecs in self-tolerance and as pattern recognition receptors in immune responses, thereby potentially providing emerging strategies for the treatment of bone related diseases.