2001 Fiscal Year Final Research Report Summary
Analysis concerning the mechanisms of differentiation in the bone marrow stromal cells after bone implantatio
| Project/Area Number |
11671429
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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 |
Orthopaedic surgery
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| Research Institution | Shinshu University |
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Principal Investigator |
TAKAOKA Kunio Shinshu University, School of Medicine, Professor, 医学部, 教授 (30112048)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Tominaga Shinshu University, School of Medicine, 医学部・附属病院, 助手 (40283270)
SAITO Naoto Shinshu University, School of Medicine, 医学部, 講師 (80283258)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Autograft / Bone formation / Bone marrow cells / BMP / Noggin / TNF-α / Pentoxifylline |
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| Research Abstract |
First, we examined the temporal and spatial expression of bone morphogenetic protein-4 ( BMP-4 ) in bone tissue and compared with that of noggin ( inhibitory factor for BMP ) in mice with fractures by means of northern blotting and in situ hybridization. BMP-4 and noggin were colocaI ized in the process of fracture repair, and expression levels of those mRNA were enhanced in the early phase.
We investigated bone formation for the bone marrow cells ( obtained from femur in rats ) in the diffusion chamber embedded to paravertebraI muscle in rats. Bone marrow cells in the diffusion chamber have attached on the inner surface on 1 or 2 weeks after implantation. And those differentiated and proliferated into chondrocytes and osteoblasts until 4 weeks after implantation. This process was similar to that of fracture repair. The expression of BMP-4 mRNA was detected in the osteoprogenitor cells, chondrocytes and osteoblasts in the diffusion chamber. These findings suggest that bone marrow cells have bone induction activity with autocrine mechanism for BMPs.
We examined about the effect for increasing bone mass by using pentoxifylline ( This drug inhibits the action of tumor necrosis factor-alpha ). The femurs in mice had osteoporotic change after administration of lipopolysaccharide ( LPS ) , but this phenomenonwas inhibited with pentoxifylline. And the effect for increasing bone mass was detected in normal mice with using pentoxifylline only. Furthermore, we confirmed that the ectopic bone induction activity with recombinant BMP-2 was enhanced by using pentoxifylline.
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