title: Dynamic Regulation of TWIST1 Expression During Chondrogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.
abstract: Human bone marrow-derived mesenchymal stem cells (BMSCs) are clinically promising to repair damaged articular cartilage. This study investigated TWIST1, an important transcriptional regulator in mesenchymal lineages, in BMSC chondrogenesis. We hypothesized that downregulation of TWIST1 expression is required for in vitro chondrogenic differentiation. Indeed, significant downregulation of TWIST1 was observed in murine skeletal progenitor cells during limb development (N = 3 embryos), and during chondrogenic differentiation of culture-expanded human articular chondrocytes (N = 3 donors) and isolated adult human BMSCs (N = 7 donors), consistent with an inhibitory effect of TWIST1 expression on chondrogenic differentiation. Silencing of TWIST1 expression in BMSCs by siRNA, however, did not improve chondrogenic differentiation potential. Interestingly, additional investigation revealed that downregulation of TWIST1 in chondrogenic BMSCs is preceded by an initial upregulation. Similar upregulation is observed in non-chondrogenic BMSCs (N = 5 donors); however, non-chondrogenic cells fail to downregulate TWIST1 expression thereafter, preventing their chondrogenic differentiation. This study describes for the first time endogenous TWIST1 expression during in vitro chondrogenic differentiation of human BMSCs, demonstrating dynamic regulation of TWIST1 expression whereby upregulation and then downregulation of TWIST1 expression are required for chondrogenic differentiation of BMSCs. Elucidation of the molecular regulation of, and by, TWIST1 will provide targets for optimization of BMSC chondrogenic differentiation culture.
authors.affiliation: 1 School of Veterinary Medicine, Veterinary Clinical Sciences, University College Dublin , Dublin, Ireland .|2 Department of Orthopaedics, Erasmus MC, University Medical Center , Rotterdam, the Netherlands .
authors.forename: Mairéad A
authors.initials: MA
authors.lastname: Cleary
authors.affiliation: 2 Department of Orthopaedics, Erasmus MC, University Medical Center , Rotterdam, the Netherlands .
authors.forename: Roberto
authors.initials: R
authors.lastname: Narcisi
authors.affiliation: 2 Department of Orthopaedics, Erasmus MC, University Medical Center , Rotterdam, the Netherlands .
authors.forename: Anna
authors.initials: A
authors.lastname: Albiero
authors.affiliation: 3 University of Veterinary Medicine Vienna , Equine Hospital, Vienna, Austria .
authors.forename: Florien
authors.initials: F
authors.lastname: Jenner
authors.affiliation: 2 Department of Orthopaedics, Erasmus MC, University Medical Center , Rotterdam, the Netherlands .|4 Department of Rheumatology, Radboud University Medical Center , Nijmegen, the Netherlands .
authors.forename: Laurie M G
authors.initials: LMG
authors.lastname: de Kroon
authors.affiliation: 5 Department of Otorhinolaryngology, Erasmus MC, University Medical Center , Rotterdam, the Netherlands .
authors.forename: Wendy J L M
authors.initials: WJLM
authors.lastname: Koevoet
authors.affiliation: 1 School of Veterinary Medicine, Veterinary Clinical Sciences, University College Dublin , Dublin, Ireland .
authors.forename: Pieter A J
authors.initials: PAJ
authors.lastname: Brama
authors.affiliation: 2 Department of Orthopaedics, Erasmus MC, University Medical Center , Rotterdam, the Netherlands .|5 Department of Otorhinolaryngology, Erasmus MC, University Medical Center , Rotterdam, the Netherlands .
authors.forename: Gerjo J V M
authors.initials: GJVM
authors.lastname: van Osch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1
keywords: TWIST1; cartilage; chondrogenesis; mesenchymal stem cells