| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Outline of Final Research Achievements |
Bone tissue is remodeled by a concerted action of osteoclastic bone resorption and osteoblastic bone formation. RANKL, an essential cytokine for osteoclast differentiation, is synthesized as a membrane-bound molecule, and cleaved into its soluble form by proteases. RANKL is critical for not only bone remodeling but also the immune organ formation. In addition, excess RANKL signal causes abnormal osteoclast activation, resulting in various bone diseases such as osteoporosis and bone metastasis. However, the functional difference between soluble and membrane-bound forms of RANKL has been poorly understood in vivo so far. In the project, we have elucidated in vivo significances of two forms of RANKL by generating mice that selectively lack each RANKL. We have demonstrated that soluble RANKL is dispensable for physiological regulation of bone and immune systems and postmenopausal osteoporosis, and that soluble RANKL has a distinct and pivotal role in bone metastases.
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