Therapeutic effects of Rosmarinic acid on osteoarthritis and analysis of mechanisms inhibiting inflammatory cartilage damage
- 주제(키워드) Osteoarthritis , MMP , NF-κB pathway , DMM , Rosmarinic acid , Sox9
- 주제(DDC) 570
- 발행기관 아주대학교 일반대학원
- 지도교수 Jung-Soon Mo
- 발행년도 2025
- 학위수여년월 2025. 8
- 학위명 석사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000035065
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Rosmarinic acid (RosA), a natural polyphenolic compound found in various medicinal herbs, is known for its anti-inflammatory and antioxidant properties. Although its anti-inflammatory activity has been reported in vitro, its effects on cartilage regeneration and in vivo osteoarthritis (OA) progression remain poorly understood. In this study, I evaluated the therapeutic role of RosA in OA using in vitro, ex vivo, and in vivo models. RosA significantly suppressed matrix metalloproteinase (MMP) expression in IL-1β stimulated chondrocytes. Mechanistically, RosA inhibited NF-κB signaling by reducing p65 phosphorylation and preventing IκB degradation, as shown by Western blotting and immunocytochemistry. In cartilage explants, RosA attenuated IL-1β induced proteoglycan loss and catabolic marker expression, confirmed by Alcian blue staining and immunohistochemistry. In a destabilization of the medial meniscus (DMM)-induced OA mouse model, intra-articular RosA preserved cartilage structure, decreased MMPs, and enhanced the expression of anabolic markers including Sox9, Col2a1, and Acan. These results suggest that RosA protects cartilage by blocking inflammatory signaling and matrix degradation while promoting anabolic activity. This study is the first to demonstrate the regenerative potential of RosA in vivo, supporting its promise as a disease-modifying OA therapy.
more목차
I. Introduction 1
II. Material and Methods 8
1. Regents and Treatments 8
2. Primary mouse articular chondrocyte culture 8
3. Cytotoxicity analysis 8
4. RNA Extraction and Amplification of Gene Transcripts by RT-PCR and qPCR 9
5. Western blotting 11
6. Culture of cartilage explants and Alcian blue staining 12
7. Induction of experimental osteoarthritis and intra-articular injection (i.a) 12
8. Cartilage tissue histology and immunohistochemistry 13
9. Immunoprecipitation (IP) 14
10. Statistical analysis 14
III. Results 16
1. RosA does not exhibit cytotoxicity in chondrocytes and suppresses IL-1β-induced catabolic factor 16
2. RosA reduces IL-1β-mediated cartilage matrix loss in cartilage explants 19
3. RosA alleviates cartilage degradation in a mouse model of DMM-induced OA 22
4. Inhibitory effects of RosA on NF-κB-mediated signaling in osteoarthritic conditions 25
5. RosA promotes cartilage matrix synthesis via upregulation of Sox9 and ECM-associated genes 28
IV. Discussion 34
V. Reference 37
국문 초록 43
