2003 Fiscal Year Final Research Report Summary
Gene therapy with serum calcium-decreasing factor, caldecrin, for osteoporosis
| Project/Area Number |
14571773
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Meikai University School of Dentistry |
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Principal Investigator |
TOMOMURA Akito Meikai University School of Dentistry, Biochemistry, Professor, 歯学部, 教授 (60188810)
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| Project Period (FY) |
2002 – 2003
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| Keywords | calcium / protease / osteoclast / gene expression / osteoporosis / ovariectomized mouse / gene therapy |
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| Research Abstract |
Bone is a dynamic tissue that is under a constant state of remodeling or homeostasis. This remodeling process is a balance between the activities of osteoblasts and osteoclasts. Interference with this balance causes osteoporosis. Osteoclast differentiation from the monocyte/macrophage lineage is influenced by local factors. RANKL/ODF/OPGL is essential for osteoclastgenesis. Serum calcium-decreasing factor, caldecrin, is a novel serine protease and suppresses matured osteoclastic bone-resorption without the protease activity. Differentiation of mouse bone-marrow derived osteoclast precursor cells was stimulated by RANKL or TNF-α. To determine whether caldecrin is potent inhibitor of osteoporosis processing, we first evaluated the effect of caldecrin on the RANKL or TNF-α stimulated osteoclastgenesis. Caldecrin suppressed mouse in vitro osteoclastgenesis. Caldecrin suppressed the increase of NFATc1 mRNA after treatment with RANKL. Thus, caldecrin suppresses mature osteoclast function and osteoclastgenesis by unknown mechanism. Next, we evaluated the effect of caldecrin gene expression in the mouse femoris muscle on the estrogen deficiency induced bone loss. At 8 weeks of age mice were either sham operated or ovariectomized, and rat caldecrin gene was expressed in the muscle for 2 weeks. The concentration of serum calcium and collagen C-peptide was decreased in the caldecrin expressed mice. Histological analysis showed that bone volume and trabecular thickness in the distal femoral cancellous bone were significantly lower in the OVX, and restored by the caldecrin gene expression. These results suggest that caldecrin is a potent inhibitor of osteoporosis.
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