Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF-β3-Associated Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells for Articular Surface Regeneration

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Emilio Satoshi HaraTakuo Kuboki

Abstract

Articular cartilage repair remains a challenging problem. Based on a high-throughput screening and functional analysis, we found that fluocinolone acetonide (FA) in combination with transforming growth factor beta 3 (TGF-β3) strongly potentiated chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). In an in vivo cartilage defect model in knee joints of immunocompromised mice, transplantation of FA/TGF-β3-treated hBMSCs could completely repair the articular surface. Analysis of the intracellular pathways revealed that FA enhanced TGF-β3-induced phosphorylation of Smad2 and Smad3. Additionally, we performed a pathway array and found that FA activates the mTORC1/AKT pathway. Chemical inhibition of mTORC1 with rapamycin substantially suppressed FA effect, and inhibition of AKT completely repressed chondrogenesis of hBMSCs. Inhibition of glucocorticoid receptor with mifepristone also suppressed FA effect, suggesting that FA involves binding to the glucocorticoid receptor. Comparative analysis with other glucocorticoids (triamcinolone acetonide [TA] and dexamethasone [DEX]) revealed the unique ability of FA to repair articular cartilage surgical defects. Analysis of intracellular pathways showed t...Continue Reading

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Citations

Jan 16, 2018·Integrative Biology : Quantitative Biosciences From Nano to Macro·Emilio Satoshi HaraTakuya Matsumoto
Jan 29, 2019·Cellular and Molecular Life Sciences : CMLS·Sheng ZhouMing Pei
Jan 25, 2019·Journal of Biomedical Materials Research. Part a·Yosuke KunitomiTakuya Matsumoto
Mar 21, 2017·Annals of the Rheumatic Diseases·Jun DaiHongwei Ouyang
Nov 6, 2018·Medicines·Norifumi H MoritaniSatoshi Kubota
Mar 9, 2020·Journal of Experimental Orthopaedics·Shuichi HamamotoNorimasa Nakamura
Mar 7, 2019·International Journal of Molecular Sciences·Yuri Hazehara-KunitomoTakuo Kuboki
Oct 14, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Emilio Satoshi HaraTakuya Matsumoto
Nov 11, 2020·Journal of Tissue Engineering and Regenerative Medicine·Masato KobayashiNorimasa Nakamura
Feb 12, 2018·ACS Biomaterials Science & Engineering·Emilio Satoshi HaraTakuya Matsumoto

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