목차

Introduction 1
Material and Methods 3
2.1. Synthesis and characterization of HA-NPs 3
2.2. Animals 4
2.3. Colorimetric assessment of terminal N-acetyl-D-glucosamine (hyaluronan breakdown products) 4
2.4. Two-photon microscopy 5
2.5. Cell culture 5
2.6. Cellular cytotoxicity assay 6
2.7. Adenovirus infection 6
2.8. Human OA cartilage and mouse model of OA 6
2.9. Histology and immunohistochemistry analyses 7
2.10. In vitro competitive inhibition and cellular uptake assays with Cy5.5-labeled free HA and HA-NPs 7
2.11. Reporter gene assay 8
2.12. PGE2 and collagenase activity assays 8
2.13. Reverse transcription-polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR) analysis 9
2.14. Western blot assays and densitometry analyses 10
2.15. Statistical analysis 11
Results 12
3.1. Characterization of self-assembled HA-NPs 12
3.2. CD44 promotes in vitro OA phenotypes in mouse primary articular chondrocytes 25
3.3. Self-assembled HA-NP mitigates IL-1β- and CD44-induced osteoarthritis phenotypes in vitro in mouse primary articular chondrocytes 31
3.4. HA-NP protects against osteoarthritic cartilage destruction in a DMM-induced OA mouse model 39
3.5. HA-NP suppresses CD44-dependent NF-κB activation in OA pathogenesis 46
Discussion 51
Reference 53