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Tankyrase inhibition stimulates innate repair capacity in osteoarthritic cartilage : 탄키라아제 억제를 통한 골관절염 연골의 내재된 회복 능력 활성화
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 김진홍 | - |
dc.contributor.author | 김수경 | - |
dc.date.accessioned | 2018-05-29T05:06:42Z | - |
dc.date.available | 2021-04-13T01:42:52Z | - |
dc.date.issued | 2018-02 | - |
dc.identifier.other | 000000150894 | - |
dc.identifier.uri | https://hdl.handle.net/10371/142441 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 자연과학대학 생명과학부, 2018. 2. 김진홍. | - |
dc.description.abstract | Osteoarthritis (OA) is a prevalent degenerative disease, which involves progressive and irreversible destruction of articular cartilage. Despite efforts to regenerate cartilage in osteoarthritic joints, it has been a difficult task as adult cartilage exhibits marginal self-repair capacity. I conducted systems-level factor analysis on mouse reference populations and identified tankyrase as a regulator of the cartilage anabolism axis. Tankyrase inhibition increases the collective expression of cartilage-specific matrix genes in mouse chondrocytes. Moreover, tankyrase inhibition stimulates chondrogenic differentiation of mesenchymal stem cells from mouse limb-bud and human bone marrow. In osteochondral defect model of rats, stem-cell transplantation coupled with tankyrase knockdown results in superior regeneration of cartilage lesions. Mechanistically, the pro-regenerative features of tankyrase inhibition are mainly triggered by regulating SOX9 transcriptional activity. I found that tankyrase binds to and poly(ADP-ribosyl)ates (PARylates) SOX9. Furthermore, in surgically induced OA mouse model, treatment of hydrogel-based tankyrase inhibitor ameliorates OA progression. These results suggest that tankyrase inhibition in treating OA cartilage may be a potential strategy for functional repair of articular cartilage. | - |
dc.description.tableofcontents | INTRODUCTION 1
MATERIALS AND METHODS 4 SUPPLEMENTARY TABLES 15 RESULTS AND FIGURES 21 DISCUSSION 41 REFERENCES 44 ABSTRACT IN KOREAN/국문초록 52 | - |
dc.format | application/pdf | - |
dc.format.extent | 5096635 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | tankyrase | - |
dc.subject | osteoarthritis | - |
dc.subject | cartilage repair | - |
dc.subject | SOX9 | - |
dc.subject | PARylation | - |
dc.subject.ddc | 570 | - |
dc.title | Tankyrase inhibition stimulates innate repair capacity in osteoarthritic cartilage | - |
dc.title.alternative | 탄키라아제 억제를 통한 골관절염 연골의 내재된 회복 능력 활성화 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Sukyeong Kim | - |
dc.description.degree | Master | - |
dc.contributor.affiliation | 자연과학대학 생명과학부 | - |
dc.date.awarded | 2018-02 | - |
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