지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학위논문
- 저자정보
- 지도교수
- 배재성.
- 발행연도
- 2017
- 저작권
- 경북대학교 논문은 저작권에 의해 보호받습니다.
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이 논문의 연구 히스토리 (4)
2017
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- 연관 학술논문 또는 학술발표를 통해 보다 발전된 연구결과를 확인하실 수 있습니다.
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Many reports have shown that sympathetic nervous system (SNS) is important for control of the bone marrow stem cell niche, however the role of neuropeptide Y (NPY) in the regulation of the bone marrow stem cell niche has not been systematically studied. Here I demonstrate that NPY deficient mice showed significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to p53-dependent apoptotic destruction of SNS fibers and/or endothelial cells. Also NPY deficient mice had impaired hematopoietic stem/progenitor cell (HSPC) mobilization due to increased expression of HSPC maintenance factors by reduction of matrix metalloproteinase-9 (MMP-9) activity in bone marrow. Pharmacological elevation of NPY prevented bone marrow impairments from chemotherapy-induced SNS injury by transforming growth factor-beta (TGF-b secreted through Y1 receptors in macrophages. NPY also led to decrease of HSPC maintenance factors expression by activating MMP-9 through the Y1 receptor osteoblasts, resulting in HSPC mobilization. Further, the mobilization of HSPCs by NPY relieved bone loss in ovariectomized mice. Therefore, these findings suggest a new roles of NPY as a regulator of the bone marrow stem cell niche, and highlight the potential therapeutic value of this neuropeptide.
목차
ABSTRACT ············································································ 1ABBREVIATIONS ···································································· 2INTRODUCTION ········································································ 3MATERIALS AND METHODS·················································· 61. Mice ············································································ 62. Regent treatments ··························································· 73. Bone marrow transplantation ·············································· 94. Flow cytometry ······························································ 105. Immunofluorescence staining of bone marrow sections ············ 126. Apoptosis assay ···························································· 137. Cell migration assay ························································ 148. Western blot ······························································· 169. Cytokine antibody assay ·················································· 1610. Quantification of sensory neuropathy by the heated-pad assay ····· 1711. Chronic stress ······························································· 1712. MMP-9 zymography ······················································ 1813. Macrophage culture ······················································· 1814. Adult schwann cell culture ················································ 1915. Osteogenic differentiation of MSCs ····································· 2016. Osteogenic differentiation ················································ 2117. Ovariectomy ································································ 2118. Bone histomorphometry ·················································· 2219. Quantitative real-time PCR ············································· 2320. Statistical analysis ·························································· 24RESULTS ················································································ 261. NPY deficiency in the HSC niche ········································· 262. Destruction of SNS fibers and/or ECs by NPY absence ··············· 363. NPY/Y1 regulation in bone marrow niche cell survival ··············· 414. The NPY/Y1 receptor pathway in bone marrow injury ················ 465. Impairment of HSPC mobilization by NPY deficiency ················ 576. HSPC mobilization by NPY ··············································· 617. The Y1 receptor in HSPC mobilization ·································· 688. The MMP-9 as a mediator on NPY/Y1 receptor induced-HSPC mobilization ····································································· 809. HSPC mobilization by endogenous NPY ································ 8510. Maintenance of bone homeostasis by NPY ····························· 88DISCUSSION ············································································ 94REFERENCES ········································································· 104ACKNOWLEDGMENTS ··························································· 112ABSTRACT IN KOREAN ·························································· 113
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