title: Co-delivery of Cbfa-1-targeting siRNA and SOX9 protein using PLGA nanoparticles to induce chondrogenesis of human mesenchymal stem cells.
abstract: During stem cell differentiation, various cellular responses occur that are mediated by transcription factors and proteins. This study evaluated the abilities of SOX9, a crucial protein during the early stage of chondrogenesis, and siRNA targeting Cbfa-1, a transcription factor that promotes osteogenesis, to stimulate chondrogenesis. Non-toxic poly-(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were coated with Cbfa-1-targeting siRNA and loaded with SOX9 protein. Coomassie blue staining and circular dichroism revealed that the loaded SOX9 protein maintained its stability and bioactivity. These NPs easily entered human mesenchymal stem cells (hMSCs) in vitro and caused them to differentiate into chondrocytes. Markers that are typically expressed in mature chondrocytes were examined. These markers were highly expressed at the mRNA and protein levels in hMSCs treated with PLGA NPs coated with Cbfa-1-targeting siRNA and loaded with SOX9 protein. By contrast, these cells did not express osteogenesis-related markers. hMSCs were injected into mice following internalization of PLGA NPs coated with Cbfa-1-targeting siRNA and loaded with SOX9 protein. When the injection site was excised, markers of chondrogenesis were found to be highly expressed at the mRNA and protein levels, similar to the in vitro results. When hMSCs internalized these NPs and were then cultured in vitro or injected into mice, chondrogenesis-related extracellular matrix components were highly expressed.
authors: Department of Biomedical Science, College of Life Science, CHA University, 3F, Yatap Ace-Core Building, 502 Yatap-Dong, Bundang-Gu, Seongnam-Si, Gyeonggi-Do 135-081, Republic of Korea.
authors: Su Yeon
authors: SY
authors: Jeon
authors: Department of Biomedical Science, College of Life Science, CHA University, 3F, Yatap Ace-Core Building, 502 Yatap-Dong, Bundang-Gu, Seongnam-Si, Gyeonggi-Do 135-081, Republic of Korea.
authors: Ji Sun
authors: JS
authors: Park
authors: Department of Biomedical Science, College of Life Science, CHA University, 3F, Yatap Ace-Core Building, 502 Yatap-Dong, Bundang-Gu, Seongnam-Si, Gyeonggi-Do 135-081, Republic of Korea.
authors: Han Na
authors: HN
authors: Yang
authors: Department of Biomedical Science, College of Life Science, CHA University, 3F, Yatap Ace-Core Building, 502 Yatap-Dong, Bundang-Gu, Seongnam-Si, Gyeonggi-Do 135-081, Republic of Korea.
authors: Hye Jin
authors: HJ
authors: Lim
authors: Department of Biomedical Science, College of Life Science, CHA University, 3F, Yatap Ace-Core Building, 502 Yatap-Dong, Bundang-Gu, Seongnam-Si, Gyeonggi-Do 135-081, Republic of Korea.
authors: Se Won
authors: SW
authors: Yi
authors: School of Integrative Engineering, Chung-Ang Univeristy, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors: Hansoo
authors: H
authors: Park
authors: Department of Biomedical Science, College of Life Science, CHA University, 3F, Yatap Ace-Core Building, 502 Yatap-Dong, Bundang-Gu, Seongnam-Si, Gyeonggi-Do 135-081, Republic of Korea. Electronic address: phd0410@hanmail.net.
authors: Keun-Hong
authors: KH
authors: Park
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis / Q000187:drug effects*; D002942:Circular Dichroism; D050659:Core Binding Factor Alpha 1 Subunit / Q000737:chemistry*; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D018014:Gene Transfer Techniques; D006025:Glycosaminoglycans / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry*; D055758:SOX9 Transcription Factor / Q000737:chemistry*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D006025:Glycosaminoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016650:Fluorescein-5-isothiocyanate
keywords: Cbfa-1; PLGA; Protein; SOX9; siRNA