| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
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| Outline of Final Research Achievements |
In some pathological conditions, skeletal muscle tissues show heterotopic ossification. Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by progressive heterotopic ossification in skeletal muscle due to a genetic mutation of ALK2, a BMP type I receptor. We found that Smad9 has unique functions among substrates of BMP receptors, such as Smad1 and Smad5. A component of NFkB signaling, p65, suppressed the Smad-dependent BMP activity by direct interaction with Smad4. Mutant ALK2 identified in patients with FOP were synergistically activated by BMP type II receptors in a kinase activity-dependent manner. These results suggest that the heterotopic ossification caused by muscle trauma in FOP might be induced by ligands activated indirectly by inflammatory reactions in the skeletal muscle.
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