|Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|Outline of Final Research Achievements
Mutations in MMP2 gene results in unique skeletal phenotype called osteolysis, which is characterized by multiple joint distraction and severe osteoporosis. The pathology of joint damages in osteolysis mimics rheumatoid synovitis, however, the underlining molecular mechanism how inactivated mutation in MMP2 results in osteolysis is largely unknown. To evaluate the possible function of mutated pro-MMP2 present in the tissue, we made expression constructs containing wild type MMP2, mutated MMP2, and wild type MT1-MMP. When co-transfected with MT1-MMP into HEK293 cells, wild type pro-MMP2 was cleaved to form an intermediate form. In contrast, when mutated MMP2 was transfected, only pro-MMP2 was visualized, indicating that mutated pro-MMP2 is resistant to the cleavage by MT1-MMP. When mutated MMP2 was co-transfected with wild type MMP2 and MT1-MMP into 293 cells, activated wild type MMP2 was decreased dose-dependently. This suggests that mutated MMP-2 may inhibit the activity of MT1-MMP.