The M-CSF receptor in osteoclasts and beyond.

Colony-stimulating factor 1 receptor (CSF1R, also known as c-FMS) is a receptor tyrosine kinase. Macrophage colony-stimulating factor (M-CSF) and IL-34 are ligands of CSF1R. CSF1R-mediated signaling is crucial for the survival, function, proliferation, and differentiation of myeloid lineage cells, including osteoclasts, monocytes/macrophages, microglia, Langerhans cells in the skin, and Paneth cells in the intestine. CSF1R also plays an important role in oocytes and trophoblastic cells in the female reproductive tract and in the maintenance and maturation of neural progenitor cells. Given that CSF1R is expressed in a wide range of myeloid cells, altered CSF1R signaling is implicated in inflammatory, neoplastic, and neurodegenerative diseases. Inhibiting CSF1R signaling through an inhibitory anti-CSF1R antibody or small molecule inhibitors that target the kinase activity of CSF1R has thus been a promising therapeutic strategy for those diseases. In this review, we cover the recent progress in our understanding of the various roles of CSF1R in osteoclasts and other myeloid cells, highlighting the therapeutic applications of CSF1R inhibitors in disease conditions. Drugs directed at a key signaling receptor involved in breaking down bone tissue could help treat diseases marked by pathological bone loss and destruction. In a review article, Kyung-Hyun Park-Min and colleagues from the Hospital for Special Surgery in New York, USA, discuss the essential roles played by the colony-stimulating factor 1 receptor (CSF1R) protein in the survival, function, proliferation and differentiation of myeloid lineage stem cells in the bone marrow, including bone-resorbing osteoclasts. They explore the links between the CSF1R-mediated signaling pathway and diseases such as cancer and neurodegeneration. The authors largely focus on bone conditions, highlighting mouse studies in which CSF1R-blocking drugs were shown to ameliorate bone loss and inflammatory symptoms in models of arthritis, osteoporosis and metastatic cancer. Clinical trials are ongoing to test therapeutic applications.