Details

Autor(en) / Beteiligte

• Baghdadi, Muhammad
• Ishikawa, Kozo
• Nakanishi, Sayaka
• Murata, Tomoki
• Umeyama, Yui
• Kobayashi, Takuto
• Kameda, Yosuke
• Endo, Hiraku
• Wada, Haruka
• Bogen, Bjarne
• Yamamoto, Satoshi
• Yamaguchi, Keisuke
• Kasahara, Ikumi
• Iwasaki, Hiroshi
• Takahata, Mutsumi
• Ibata, Makoto
• Takahashi, Shuichiro
• Goto, Hideki
• Teshima, Takanori
• Seino, Ken-ichiro

Titel

A role for IL-34 in osteolytic disease of multiple myeloma

Ist Teil von

• Blood advances, 2019-02, Vol.3 (4), p.541-551

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Multiple myeloma (MM) is a hematological malignancy that grows in multiple sites of the axial skeleton and causes debilitating osteolytic disease. Interleukin-34 (IL-34) is a newly discovered cytokine that acts as a ligand of colony-stimulating factor-1 (CSF-1) receptor and can replace CSF-1 for osteoclast differentiation. In this study, we identify IL-34 as an osteoclastogenic cytokine that accelerates osteolytic disease in MM. IL-34 was found to be expressed in the murine MM cell line MOPC315.BM, and the expression of IL-34 was enhanced by stimulation with proinflammatory cytokines or by bone marrow (BM) stromal cells. MM-cell–derived IL-34 promoted osteoclast formation from mouse BM cells in vitro. Targeting Il34 by specific small interfering RNA impaired osteoclast formation in vitro and attenuated osteolytic disease in vivo. In BM aspirates from MM patients, the expression levels of IL-34 in CD138+ populations vary among patients from high to weak to absent. MM cell–derived IL-34 promoted osteoclast formation from human CD14+ monocytes, which was reduced by a neutralizing antibody against IL-34. Taken together, this study describes for the first time the expression of IL-34 in MM cells, indicating that it may enhance osteolysis and suggesting IL-34 as a potential therapeutic target to control pathological osteoclastogenesis in MM patients. Osteolytic bone disease is one of the most disabling complications of multiple myeloma that leads to significant morbidity and occasionally mortality. In the report by Seino and colleagues, the role of interleukin-34, a ligand of colony stimulating factor 1, in osteolytic bone disease in multiple myeloma is evaluated with provocative findings that potentially identifies a novel clinical target for controlling this common complication of this disease. [Display omitted]