Osteoimmunology: the expanding role of immunoreceptors in osteoclasts and bone remodeling.

The study of bone and immunology (termed osteoimmunology) has led to the discovery of many important similarities between the two systems including shared niches, mechanisms, cytokines and receptors. The bone marrow provides a niche for hematopoietic cells including those of the lymphoid and myeloid lineage. Osteoclasts, specialized polykarons arising from myeloid precursors, bind to bone and resorb the organic and inorganic components through secretion of acid and proteases. Osteoclasts are differentiated and activated by cytokines that can be produced by immune cells and osteoclast activity can be dysregulated in states of autoimmunity or high inflammation. Similar to B and T cells, osteoclasts require coordinated co-stimulation of signaling pathways provided in the form of receptor-associated immunoreceptor tyrosine-based activation motif adaptor proteins, DAP12 and FcRγ, to drive differentiation and activation. In this review, we will cover the differentiation process of osteoclasts from the earliest precursors shown to have differentiation potential and the signals needed to drive these cells into osteoclast commitment and activation.