Elucidation of molecular mechanism of the regulation of skeletal homeostasis, and development of new therapeutic approaches against skeletal disorders

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293215
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: The University of Tokushima
• Principal Investigator: MATSUMOTO Toshio 徳島大学, 藤井節郎記念医科学センター, 副理事 (20157374)
• Co-Investigator(Kenkyū-buntansha): FUKUMOTO Seiji 徳島大学, 藤井節郎記念医科学センター, 特任教授 (30202287) ; ABE Masahiro 徳島大学, 大学院医歯薬学研究部, 教授 (80263812)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: インターロイキン-11 (IL-11) / Wntシグナル / 骨芽細胞 / 脂肪細胞 / 骨髄腫 / 破骨細胞 / Pim-2

Outline of Final Research Achievements

IL-11 regulates osteoblast/adipocyte differentiation via Wnt signaling. In order to clarify the role of IL-11 on the regulation of osteogenesis and adipogenesis, we created IL-11 knockout mice. These mice exhibited reduced bone mass due to suppressed bone formation, along with increased adipose tissue mass with insulin resistance and glucose intolerance. These results demonstrate the important role of IL-11 in the regulation of osteoblast/adipocyte differentiation.
Interaction of myeloma cells with bone cells enhanced Pim-2 expression in myeloma cells, and Pim-2 enhanced survival and drug resistance of myeloma cells. Myeloma cell-osteoblast interaction also enhanced Pim-2 expression in osteoblasts, which suppressed osteoblast differentiation. Furthermore, Pim inhibitors potently suppressed myeloma growth and enhanced bone formation. These observations suggest that inhibition of Pim-2 may become a new therapeutic approach against multiple myeloma.

Free Research Field

内分泌代謝学、骨代謝学