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

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

“…OPG is then a strong inhibitor of osteoclast differentiation/activation and bone degradation. Whether RANKL is mandatory to osteoclastogenesis as revealed by the marked osteopetrotic phenotype of RANKL-deficient mice [20], M-CSF can be substituted by various other soluble mediators defining a M-CSF-dependent canonical and a M-CSF-independent non-canonical pathway of osteoclastogenesis [21,22]. However, the RANKL/RANK/OPG system is not restricted to the bone tissue and is also involved in the control of angiogenesis and immune system [19].…”

BYL719, a new α‐specific PI3K inhibitor: Single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma

“…CD14 1 cells (purity around 96%) were isolated from human peripheral blood, using MACS microbeads (Miltenyi Biotec, Germany) as previously described. 32,33 a-MEM (Lonza) containing 10% FCS, 25 ng/mL human macrophage colony stimulating factor (hM-CSF; R&D Systems) and 100 ng/mL human receptor activator of nuclear factor kappaB ligand (hRANKL; R&D Systems) were changed every 3 days. After 11 days of culture for the CD14 1 cells, osteoclasts were visualized by means of TRAP staining (Sigma).…”

IL-34 a Newly Discovered Cytokine

“…They are multifunctional proteins which have a role in both innate and adaptive immune responses (8-13) with an effect on proliferation, differentiation, inhibition, apoptosis and chemoattraction (14-16). In addition, cytokines are involved in and mediate many different diseases (17-18).The newly-characterized Interleukin-34 (IL-34) plays a central role in innate immunity and adaptive immunity, and is an important molecule for the communication between cells, tissues, and organs.Recently it has been reported that interleukin-34 (lL-34) stimulates monocyte viability but does not affect responses in a wide spectrum ofother assays (20)(21)(22)(23)(24)(25). In both in vitro and in vivo studies, IL-34 directly modulates the number and function of monocytes and regulates myeloid cell growth and differentiation.…”

“…Recently it has been reported that interleukin-34 (lL-34) stimulates monocyte viability but does not affect responses in a wide spectrum ofother assays (20)(21)(22)(23)(24)(25). In both in vitro and in vivo studies, IL-34 directly modulates the number and function of monocytes and regulates myeloid cell growth and differentiation.…”

“…In both in vitro and in vivo studies, IL-34 directly modulates the number and function of monocytes and regulates myeloid cell growth and differentiation. We believe that the immunological effects of IL-34 candidate this interleukin as an immunotherapeutic agent for the treatment of several different diseases (20,(26)(27)(28)(29)(30)(31)(32)(33)(34). To discover the receptor for IL-34, a collection ofextracellular domains oftrans-membrane proteins has been used which is a known cytokine receptor called colony-stimulating factor 1 receptor or macrophage colony-stimulating factor receptor (35)(36)(37)(38).…”