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The discovery of a common factor affecting Osteoarthritis and Parkinson's disease

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dc.contributor.author조, 찬미-
dc.date.accessioned2023-11-16T05:43:57Z-
dc.date.available2023-11-16T05:43:57Z-
dc.date.issued2023-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/26849-
dc.language.isoen-
dc.titleThe discovery of a common factor affecting Osteoarthritis and Parkinson's disease-
dc.typeThesis-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000032442-
dc.subject.keywordOsteoarthritis-
dc.subject.keywordDJ1-
dc.subject.keywordSNCG-
dc.subject.keywordCD44-
dc.subject.keywordLevNPs-
dc.description.degreeDoctor-
dc.contributor.department대학원 의생명과학과-
dc.contributor.affiliatedAuthor조, 찬미-
dc.date.awarded2023-
dc.type.localTheses-
dc.citation.date2023-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.description.tableOfContentsI. Introduction 1

1. Osteoarthritis and chondrocytes 1

2. Osteoarthritis and Parkinson’s disease 2

3. DJ1 and synuclein in Parkinson’s disease 4

4. Treatment of Osteoarthritis 6

5. CD44 in Osteoarthritis 7

6. Nanoparticle therapy and Levan 8

7. Aim of this study 9

II. Material and Methods 11

Human OA cartilage 11

Primary articular mouse chondrocyte culture 11

Cell viability analysis 13

RT-PCR and qRT-PCR 13

Western blot analysis 14

Experimental OA in mice 15

Preparation of LevNP 16

Chondrocyte explant culture and Alcian blue staining 17

Cartilage Tissue Histology, Immunohistochemistry Analyses, and Fluorescence Distribution

Analyses 17

Confocal microarray imaging 19

Protein array 19

In silico chemical-protein binding assay 20

In silico analysis, microarray, and Ingenuity Pathway Analysis (IPA) 20

Statistical analysis 21

III. Results 22

Part I_The discovery of common disease factor between Parkinson’s disease and Osteoarthritis 22

Identification of common genes between PD and OA 22

Expression of DJ1 decreased in human and mouse OA cartilages 25

DJ1 depletion regulates OA-related factors in articular chondrocytes 25

DJ1 deficiency in cartilage tissue causes OA pathogenesis in mice 30

The identification of a down-mediator of DJ1 33

DJ1-induced γ-synuclein modulates OA Pathogenesis 36

γ-synuclein knockout in mice inhibits experimental OA pathogenesis 43

Secreted γ-synucleins affect chondrocytes in an autocrine manner 45

Identification of drugs that correlate with γ-synuclein expression using CMap 49

PART Ⅱ_ Nanotherapeutic material for OA treatment 51

Anti-Inflammatory Activity of LevNPs 51

Interaction Between LevNPs and CD44 53

Blockade of CD44 Protects Catabolic Factor Expression During OA Pathogenesis 57

Penetration Efficacy and Function of LevNPs in Mouse Cartilage 61

LevNPs reduce IL-1β induced ECM degradation and promote ECM synthesis in cartilage 67

Protection Against OA Pathogenesis via Intra-Articular Injection of LevNPs in Posttraumatic OA 69

IV. Discussion 73

V. Reference 84

국문 초록 99
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