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동물 모델의 초기 진단 및 골관절염 조절에 의한 치료 효능평가 연구
- Alternative Title
- Byoung Ju Kim
- Author(s)
- Kim, Byung Ju
- Alternative Author(s)
- Byoung Ju Kim
- Advisor
- 민병현
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2014-02
- Language
- eng
- Keyword
- Osteoarthritis; animal model; destabilization of medial meniscus (DMM); subchondral bone change; cartilage degeneration; hyaluronic acid (HA); Micro-CT; Type II collagen; Immuno-liposomes
- Alternative Abstract
- Osteoarthritis (OA) is a multifactorial disease with many risk factors and it results from a complex interplay between mechanical, cellular and biochemical forces. Animal models of OA are an important surrogate that provides a means to study OA pathophysiology, and develop therapeutic agents and biomarkers for diagnosing and prognosing OA. CHAPTER I: Osteoarthritis (OA) is a multifactorial disease affecting both the cartilage and the subchondral bone. However, animal models of OA cannot represent both of the changes and show variations depending on induction methods and animal species/strains. This study first investigated subchondral bone changes and its correlation with cartilage degeneration in two different OA models in C57Bl/6 mice. Experimental OA was produced by type II collagenase-induced osteoarthritis (CIOA) and destabilization of the medial meniscus (DMM). The subchondral plate and trabecular bone of the tibia were analyzed by micro-computed tomography (µCT) and cartilage degeneration was analyzed histologically after safranin-O staining at 2, 4, 6 and 8 weeks. In DMM model, cartilage degeneration was induced reproducibly and progressively along with time. Progressive increase in subchondral bone volume but not in bone thickness was also observed in both subchondral bone plate (SBP) and subchondral trabecular bone (STB) in the medial tibial area. The changes in subchondral bone volume was correlated well with the histological cartilage degeneration (R2=0.7870). In contrast to CIOA model, cartilage degeneration was not relatively unpredictable with being increased only until 4 weeks and decreased thereafter. No significant changes in subchondral bone were observed in all area at all time points. These results suggest that DMM model of mice OA is more reliable and useful than CIOA model by representing better both of cartilage degeneration and subchondral bone change with high correlation coefficient. CHAPTER II: We established an OA model of C57BL/6 mice that is more reproducible and amenable to therapeutic intervention by controlling their movement. OA was induced in 9 week-old C57BL/6 mice by destabilizing the medial meniscus (DMM). The mice were then raised either in the standard cage for free movement or in a confine cage customized to restrict mice movement. Mice in the confine cage were subjected to no exercise or an exercise of 400, 800 and 1200 m/day, respectively. OA lesions of mice in confine cage were much severer in the exercise group and showed much less variation. The validity of our novel OA model with the movement control system was proven by successfully discriminating the therapeutic effect of hyaluronic acid (HA) in the histological scores, while the OA model using standard cage showed just statistically insignificant difference. In conclusion, the mice OA model could be more reproducible and reliable by adopting the confine cage and enforced periodic exercise of mice. CHAPTER III: The extracellular matrix (ECM) of cartilage is dense, avascular and aneurogenic tissues, these early lesions are not painful and often go undetected until significant damage has occurred. At present, there are no appropriate treatments to cure cartilage degradation so early detection is critical. One of the cause of limitation for developing a preventive therapy for OA is the lack of good tools for efficiently diagnosing the disease and monitoring its progression during the early stages. We have developed MabCII (monoclonal antibody collagen type II) nanosomes encapsulated the XenoFluor dye for diagnosis of early OA. These MabCII-nanosomes increased the binding efficacy to tissue according to the severity of cartilage damage. Here, we show that MabCII-nanosomes can monitor sensitively identify minimal cartilage damage in the DMM (destabilization of the medial meniscus) model of OA. In conclusion, MabCII-nanosomes techniques could potentially be used non-invasive method for diagnosis the early onset of osteoarthritis disease. In conclusion, our results suggest that developed osteoarthritis model and diagnostic tools could be a useful tool for various therapeutic applications instead of human on regenerative medicine field.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 4. Theses(Ph.D)
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