Title

新型小分子化合物對於間質幹細胞年齡依賴性分化之影響

Translated Titles

The effects of novel small molecule compounds on age-dependent differentiation of mesenchymal stem cells

Authors

邱俊嘉

Key Words

間質幹細胞 ; 小分子化合物 ; 成骨細胞 ; 脂肪細胞 ; mesenchymal stem cell ; small molecule compound ; osteoblast ; adipocyte

PublicationName

中興大學生命科學系所學位論文

Volume or Term/Year and Month of Publication

2018年

Academic Degree Category

碩士

Advisor

李龍緣

Content Language

繁體中文

Chinese Abstract

人類骨髓間質幹細胞 (Human Bone marrow-derived mesenchymal stem cells ,hBM-MSC ) 是脂肪細胞與成骨細胞共同的前體細胞。我們實驗室先前的研究發現,不管在人類或是老鼠中分離出來的 MSCs都顯示出會隨著老化而降低其成骨分化能力並且提高脂肪細胞分化,這個結果導致它們之間分化平衡發生改變,有可能會造成骨質鬆與肥胖症的發生。在本研究中要探討新型小分子化合物20及化合物17 (compound 20/17) 是否會影響其MSCs分化能力,同時也與目前骨質疏鬆症臨床用藥strontium ranelate ( SrR ) 來進行比較。本論文的研究結果顯示,在人類骨髓間質幹細胞株與老鼠骨髓所分離的MSCs中,不管是在早期年輕或晚期年老的細胞或者是不同年齡老鼠所分離出來的骨髓間質幹細胞,在處理化合物20後其成骨分化顯著的提高同時也抑制脂肪分化的形成;相反地處理化合物17後其成骨細胞分化被抑制並且促進脂肪細胞的形成。此外,處理化合物20後促進MSC成骨細胞分化的效果比strontium ranelate好得多。本研究目前在體外的實驗中都顯示出了化合物20提升成骨和抑制脂肪分化的能力良好,未來可以進行動物試驗,近一步證明化合物20的功效,期望可提供未來臨床骨質疏鬆症治療一種新型用藥。

English Abstract

Osteoblasts and adipocytes are derived from a common precursor, human bone marrow-derived mesenchymal stem cell (hBM-MSC). Previously, we have demonstrated that MSCs isolated from human or mice showed decreased osteogenic potential and increased adipogenic potential with aging. This results in altering the normal fate of differentiating MSCs, and may lead to the development of obesity and osteoporosis. In this study, we focus on whether novel compounds 20 and 17 will affect MSC differentiation, and compare their effect with a current clinical osteoporosis drug, strontium ranelate. Our data demonstrate that after treating human mesenchymal stem cell line and mice MSCs at different passages or ages with compound 20, the adipogenic potential of MSCs declined significantly but the osteogenic potential rose markedly. Conversely, after treatment of compound 17, the osteogenic differentiation potential of MSCs declined significantly but the adipogenic potential rose markedly. Moreover, the effect of compound 20 on the osteogenic differentiation of MSCs is much better than strontium ranelate. Our in vitro experiments conclude that compound 20 decreases adipogenesis and increases osteogenesis of MSCs. In the future, we can examine in vivo experiment to further prove the efficacy of compound 20, which may provide a new type of drug for osteoporosis treatment.

Topic Category 生命科學院 > 生命科學系所
生物農學 > 生物科學
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