| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Outline of Final Research Achievements |
We analyzed the limb development of mesenchymal-specific TGF-beta type I receptor (ALK5) mutant mice by Dermo1-Cre in order to identify the role of TGF-beta signaling in cartilage formation and matrix remodeling. Femurs of ALK5Dermo1CKO mice were significantly shorter than those of control mice. In primary spongiosa of E18.5 ALK5Dermo1CKO femurs, the cartilage matrix was remained , TRAP-positive osteoclasts were decreased, and RANKL expression by osteoblasts was substantially reduced. Since Dermo1-Cre was not expressed in hematopoietic lineage cells, the decreased number of mature osteoclasts in the primary spongiosa of ALK5Dermo1CKO femurs is likely due to reduced RANKL-mediated osteoclast differentiation. Our results suggest that TGF-beta signaling is required for cartilage matrix remodeling during endochondral ossification by promoting osteoclastogenesis in an osteoblast-dependent manner.
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