목차

I. 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