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Functional characterization of activin A-activin receptor IIB pathway in osteoarthritis
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 양, 시영 | - |
| dc.contributor.author | 전, 지민 | - |
| dc.date.accessioned | 2021-01-06T02:34:36Z | - |
| dc.date.available | 2021-01-06T02:34:36Z | - |
| dc.date.issued | 2020 | - |
| dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/19223 | - |
| dc.description.abstract | 비공개 | - |
| dc.description.tableofcontents | I. Introduction 1
1. Osteoarthritis 1 2. Cartilage and osteoarthritis 2 3. Treatment of osteoarthritis 3 4. Activin receptor IIB (ACVR2B) and ligands 5 5. 3'-Sialylllactose 6 6. Aim of this study 8 II. Material and Methods 9 Primary articular mouse chondrocytes culture 9 Human OA cartilage 10 RT-PCR and qRT-PCR 10 Immunoprecipitation analysis and Western blot 12 Experimental OA in mice 13 Histology and immunohistochemistry 14 Collagenase activity and PGE2 assay 15 Detection of ROS 16 In silico analysis, microarray, and Ingenuity Pathway Analysis (IPA) 16 Viability analysis 18 LS-MS experiments 18 Statistical analysis 19 III. Results 20 Part I_Therapeutic target 20 Identification of novel pathogenic receptor in osteoarthritic development 20 Activin receptor IIB increases in human and mouse OA cartilage 26 Inhibited Activin receptor IIB attenuate cartilage destruction in OA development 26 Increased activin A, an Activin receptor IIB ligand, promotes OA pathogenesis 31 Activin A depletion inhibits cartilage damage by inhibiting catabolic factors 36 NOX4 mediated activin A regulates catabolic factor 39 NOX4 is required for activin A induced OA pathogenesis in mice 44 Mechanism underlying activin A-mediated NOX4-induced catabolic factor expression 49 Systemic activin receptor IIB inhibition attenuates cartilage destruction in OA development 52 Part II_ Prophylactic agent 57 3'-sialyllactose increased Col2a1 synthesis in chondrocytes 57 3′-sialyllactose blocks proinflammatory cytokines induced Mmp3, Mmp13 and Cox2 expression 62 Both activation of Sox9 and inhibition of NF-κB are regulated by 3'-sialyllactose in chondrocytes 67 Oral administration of 3'-sialyllactose protects cartilage destruction in the OA model 69 3'-sialyllactose modulates ERK and NF-κB signaling pathways for anabolic and catabolic factor expression 73 IV. Discussion 75 V. Reference 88 국문 초록 104 | - |
| dc.language.iso | en | - |
| dc.title | Functional characterization of activin A-activin receptor IIB pathway in osteoarthritis | - |
| dc.type | Thesis | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000030209 | - |
| dc.subject.keyword | Osteoarthritis | - |
| dc.subject.keyword | Chondrocytes | - |
| dc.subject.keyword | Activin receptor IIB | - |
| dc.subject.keyword | Activin A | - |
| dc.subject.keyword | 3'-Sialyllactose | - |
| dc.subject.keyword | activing receptor IIB | - |
| dc.subject.keyword | 퇴행성관절염 | - |
| dc.subject.keyword | 연골세포 | - |
| dc.description.degree | Doctor | - |
| dc.contributor.department | 대학원 의생명과학과 | - |
| dc.contributor.affiliatedAuthor | 전, 지민 | - |
| dc.date.awarded | 2020 | - |
| dc.type.local | Theses | - |
| dc.citation.date | 2020 | - |
| dc.embargo.liftdate | 9999-12-31 | - |
| dc.embargo.terms | 9999-12-31 | - |
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