Controlling unruly osteoclasts

Monocytes beget macrophages, and fused macrophages beget bone-resorbing osteoclasts. Factors such as monocyte-colony stimulating factor (from stromal cells) and interleukin-1 (IL-1; from macrophages) keep this process ticking along, but now Li and colleagues report (page 1169) that osteoclasts make a protein that forms part of a critical feedback loop. Without the IRAK-M (IL-1 receptor associated kinase M) protein, which was previously thought to be expressed only in macrophages, osteoclasts are hyperactivated and mice get severe osteoporosis.

Bone maintenance depends on the coordination of bone formation by osteoblasts and bone resorption by osteoclasts. Li et al., prompted by the description of IRAK-M as a macrophage-specific inhibitor of signals from the IL-1 and Toll-like receptors, examined the function of this protein in osteoclasts. They found that mice lacking IRAK-M had increased numbers of osteoclasts, which...