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dc.description.abstractBone resorption and remodeling is a controlled, physiological process that requires the function of osteoclasts. An important issue for bone remodeling is to identify factors that regulate bone homeostasis. Although p202 is known to be RANKL-inducible gene whose expression is notably decreased in cells expressing a dominant interfering mutant of Rac1, the function of p202 in osteoclastogenesis is unknown. I found that IFN-β was not induced in Rac1-dominant negative mutant cells. I also showed that p202 was down-regulated in IFNAR-deficient bone marrow monocyte/macrophage cells (BMMs) in response to RANKL stimulation. These data suggested that RANKL induces p202 expression via Rac1-IFN-β-dependent pathway. Overexpression of p202 in BMMs inhibits the formation of TRAP positive multinuclear osteoclasts. Furthermore, I found that p202 interacted with NFATc1, a key osteoclastic transcription factor. Overexpression of p202 inhibited the transcriptional activity of NFATc1. Thus, p202 may represent a key negative regulator for osteoclast formation.;뼈 형성과정에서 파골세포의 분화가 과다하면 균형이 깨져 뼈 관련 질환이 발생할 수 있다. 따라서 파골세포 분화를 조절하는 인자를 찾는 것은 중요하다. p202는 interferon(IFN)에 의해 발현되는 단백질로, p202 유전자는 1번 염색체에 위치하고 있다. p202는 세포의 성장과 증식을 억제하는 역할을 한다고 잘 알려져 있지만 파골세포에서의 역할은 알려져 있지 않다. 위 실험에서 p202가 RANKL에 의해 발현된 Rac1, Rac1에 의해 발현된 IFN-β를 통해 발현됨을 알 수 있었다. 또한, p202를 BMMs에 과발현 시키고 M-CSF와 RANKL을 처리해 주었을 때 p202를 과발현 시키지 않은 BMMs에 비해 파골세포의 분화가 억제되는 것을 볼 수 있었다. GST pull down assay를 통해 p202가 파골세포 분화에 중요한 인자인 NFATc1과 결합하면서 NFATc1의 전사를 억제함을 확인하였다. 이러한 결과들은 p202가 파골세포 분화를 조절하는 중요한 역할을 할 것임을 시사한다.-
dc.description.tableofcontentsI. INTRODUCTION 1 II. EXPERIMENTAL PROCEDURES 6 1. Reagents and constructs 6 2. Generation of osteoclast precursor cells 6 3. Northern blot analysis 7 4. Reverse transcription-polymerase chain reaction (RT-PCR) 7 5. Preparation of GST fusion proteins and protein interaction assay 8 6. Transfection and luciferase assay 9 7. Preparation of retrovirus and infection of BMMs 10 8. In vitro assay for osteoclast formation 10 9. Western blot analysis 11 III. RESULTS 12 1. p202 is induced by IFN-β in a Rac1 dependent manner 12 2. p202 is induced by IFN-α and IFN-β 15 3. p202 expression is down-regulated by blocking the IFN-α and IFN-β signal with neutralizing antibody 17 4. The induction of p202 is reduced in IFNAR knockout mouse 19 5. Overexpression of p202 inhibits osteoclastogenesis 21 6. p202 interacts with NFATc1 24 7. p202 inhibits transactivation of NFATc1 27 IV. DISCUSSION 29 V. REFERENCES 33 VI. 논문개요 39-
dc.format.extent1551396 bytes-
dc.publisher이화여자대학교 대학원-
dc.titlep202 negatively regulates RANKL-mediated osteoclast differentiation-
dc.typeMaster's Thesis-
dc.title.translated파골세포 분화 과정에서 p202 의 역할-
dc.creator.othernameJung, Hyun Ju-
dc.format.pageiv, 40 p.-
dc.identifier.major대학원 생명·약학부생명과학전공- 8-
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