DC-STAMP: A Key Regulator in Osteoclast Differentiation

Osteoimmunology research is a new emerging research field that investigates the links between the bone and immune responses. Results from osteoimmunology studies suggest that bone is not only an essential component of the musculoskeletal system, but is also actively involved in immune regulation. Many important factors involved in immune regulation also participate in bone homeostasis. Bone homeostasis is achieved by a coordinated action between bone-synthesizing osteoblasts and bone-degrading osteoclasts. An imbalanced action between osteoblasts and osteoclasts often results in pathological bone diseases: osteoporosis is caused by an excessive osteoclast activity, whereas osteopetrosis results from an increased osteoblast activity. This review focuses on dendritic cell-specific transmembrane protein (DC-STAMP), an important protein currently considered as a master regulator of osteoclastogenesis. Of clinical relevance, the frequency of circulating DC-STAMP+ cells is elevated during the pathogenesis of psoriatic diseases. Intriguingly, recent results suggest that DC-STAMP also plays an imperative role in bone homeostasis by regulating the differentiation of both osteoclasts and osteoblasts. This article summarizes our current knowledge on DC-STAMP by focusing on its interacting proteins, its regulation on osteoclastogenesis-related genes, its possible involvement in immunoreceptor tyrosine-based inhibitory motif (ITIM)-mediated signaling cascade, and its potential of developing therapeutics for clinical applications. J. Cell. Physiol. 231: 2402-2407, 2016. © 2016 Wiley Periodicals, Inc.