Beyond bone: the emerging role of osteoclasts in immune regulation, leukemia development and following myeloablative therapy

Osteoclasts are important regulators of bone remodeling, with an established role in maintaining skeletal homeostasis. The emergence of osteoimmunology has identified osteoclasts as key players in the immune system. In particular, osteoclasts can initiate bi-directional crosstalk mechanisms with hematopoietic stem cells and various immune cells, such as T cells, B cells and NK cells, to influence hematopoiesis and inflammatory response. In recent years, emerging evidence suggests that osteoclasts can remodel the leukemia bone marrow niche, contributing to both leukemogenesis and leukemia-induced bone destruction. In addition, osteoclasts have been implicated as a major source of bone loss following myeloablative therapy for hematopoietic stem cell transplant. An understanding of the mechanisms by which osteoclasts contribute to leukemia-induced and post myeloablative therapy bone loss could pave way for development of new therapeutic approaches in the near future.