1996 Fiscal Year Final Research Report Summary
Regulation of osteoblastic differentiation and its implication in involutional osteoporosis
| Project/Area Number |
07671111
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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 |
内分泌・代謝学
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| Research Institution | University of Tokyo |
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Principal Investigator |
TAKEUCHI Yasuhiro University of Tokuo, Faculty of Medicine, Assistant Professor, 医学部・附属病院(分), 助手 (50202164)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUMOTO Seiji University of Tokuo, Faculty of Medicine, Assistant Professor, 医学部・附属病院(分), 助手 (30202287)
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| Project Period (FY) |
1995 – 1996
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| Keywords | osteoblast / aging / osteoporosis / matrix proteins / collagen / integrin / adhesion molecules / bone marrow cells |
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| Research Abstract |
Modulation of TGF-beta actions in osteoblasts by bone matrix proteins
We demonstrated that decorin, a bone matrix protein synthesized by osteoblasts, binds TGF-beta and enhances the binding to its receptors on osteoblastic cells, resulting in the augmentation of bioactivity of TGF-beta. Thus, decorin is not only a component of bone matrix but may be involved in the bone formation that is stimulated by TGF-beta.
Involvement of collagen-integrin interactions in osteoblastic differentiation
Interactions of osteoblastic cells to type I collagen (COL) via alpha2beta1 integrin were shown to be required for osteoblastic differentiation. The binding of COL to the integrin provoked tyrosine phosphorylation and activation of focal adhesion kinase (FAK) and ERK,a member of MAP kinase family. Several inhibitors that inhibit FAK suppressed collagen-induced osteoblastic differentiation. Furthermore, decrease in FAK expression with the stable expression of antisense mRNA for FAK disrupted both ERK activ
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ation and osteoblastic differentiation. Because transient expression of protein phosphatase CL100 that inactivates ERK prevented the differentiation, the direct involvement of ERK was suggested. These observations indicate that cell-matrix interactions, especially COL-integrin interactions, are essentially involved in the osteoblastic differentiation via activations of signaling cascades directly associated with the integrin, FAK and ERK.
Osteoblastic differentiation in bone marrow cells in advancing with age
P6 strain of senescence-accerelated mice (SAM) is a murine model of involutional osteoporosis. We showed that osteoblastogenesis of bone marrow stromal cells was impaired in SAMP6 mice compared with the control SAMR1 mice. Treatment with interleukin (IL)-11 could restore this disturbance. We further showed that IL-11 expression in bone marrow cells of SAMP6 was less than that of SAMR1, suggesting that insufficient IL-11 actions causes the impaired osteoblastogenesis in SAMP6. Thus, a decrease in actions of cytokines like IL-11 is further to be investigated for the pathogenesis of involutional osteoporosis. Less
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Research Products
(12 results)
