Interleukin-34 is expressed by giant cell tumours of bone and plays a key role in rankl-induced osteoclastogenesis

IL-34 and M-CSF form a novel heteromeric cytokine and regulate the M-CSF receptor activation and localization

“…1B). In addition, as shown previously [8], M-CSF and IL-34 similarly induced RANKL-associated osteoclastogenesis in a dose-dependent manner and the combination of M-CSF and IL-34 did not reveal any competitive or additive activity between these cytokines ( Supplementary Fig. 2).…”

“…In addition to the already identified functions of IL-34 and M-CSF in exacerbated macrophage activation (bowel diseases, liver fibrosis, chronic skin inflammation, arthritis, etc. ), this new heteromeric cytokine M-CSF/IL-34 which may differentially regulates the activation/localization of M-CSFR strengthens the global therapeutic approaches for blocking all biological functions coming from these molecules [7,8,[45][46][47][48][49][50][51].…”

“…More specifically, macrophage polarization induced by M-CSF and IL-34 is similar, as both cytokines lead to immunosuppressive macrophages M2 [7]. In addition, IL-34 promotes osteoclastic differentiation with almost the same efficiency as M-CSF [8]. However, IL-34 may also display singular functions, as supported by a different expression pattern of M-CSF and IL-34 during brain development, thus suggesting complementary activities for these ''twins'' [9].…”

Interleukin-34, a comprehensive review

“…Since IL‐34 is expressed at mRNA level in various tissues, this expression is expected to be changed under pathological conditions. Indeed, several studies have confirmed the enhancement of IL‐34 expression at mRNA and protein levels in the context of various diseases including autoimmune disorders, inflammation, infections, metabolic diseases, neurological disorders, and cancer . At the cellular level, IL‐34‐producing cells include synovial fibroblasts, immune cells, epithelial cells, endothelial cells, adipocytes, and cancer cells.…”

Osteoclasts

“…Nevertheless, the fact that administration of M-CSF to the op/op mouse and rat which cannot produce M-CSF, rescues the bone phenotype [17,18] speaks to the major role played by this molecule in osteoclast biology. Of interest, IL-34 is secreted at high levels by the stromal, presumptively oncogenic, component of giant cell tumor of bone [19], helping to explain why patients exhibiting this condition have marked lytic capacity. Finally, while M-CSF and RANKL are the basal proteins necessary to generate and activate osteoclasts, a range of secondary stimulators also play an important role in the same process.…”