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Functional characterization of activin A-activin receptor IIB pathway in osteoarthritis

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dc.contributor.author전, 지민-
dc.date.accessioned2021-01-06T02:34:36Z-
dc.date.available2021-01-06T02:34:36Z-
dc.date.issued2020-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/19223-
dc.description.abstract비공개-
dc.description.tableofcontentsI. 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
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dc.language.isoen-
dc.titleFunctional characterization of activin A-activin receptor IIB pathway in osteoarthritis-
dc.typeThesis-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000030209-
dc.subject.keywordOsteoarthritis-
dc.subject.keywordChondrocytes-
dc.subject.keywordActivin receptor IIB-
dc.subject.keywordActivin A-
dc.subject.keyword3'-Sialyllactose-
dc.subject.keywordactiving receptor IIB-
dc.subject.keyword퇴행성관절염-
dc.subject.keyword연골세포-
dc.description.degreeDoctor-
dc.contributor.department대학원 의생명과학과-
dc.contributor.affiliatedAuthor전, 지민-
dc.date.awarded2020-
dc.type.localTheses-
dc.citation.date2020-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
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