Interleukin-34: An enigmatic cytokine

Macrophage colony-stimulating factor (M-CSF) is required for the differentiation, proliferation and survival of cells of the monocyte lineage. M-CSF deficiency in mice (op/op mice) leads to a specific phenotype including skeletal deformities, a lack of teeth, and a marked osteopetrosis explained by an absence of osteoclasts. Recently, a novel cytokine, interleukin-34 (IL-34), has been discovered and shares a common receptor with M-CSF, resulting in functional overlaps in bone (similar effect on osteoclastogenesis) and in inflammatory systems (monocyte proliferation, and upmodulation of chemokine production). This Perspective focuses on the biology of IL-34 as suggested by recent published data and discusses IL-34's potential role in bone pathophysiology.