title: DEC2 is a negative regulator for the proliferation and differentiation of chondrocyte lineage-committed mesenchymal stem cells.
abstract: Differentiated embryo chondrocyte 2 (DEC2) is a basic helix-loop-helix-Orange transcription factor that regulates cell differentiation in various mammalian tissues. DEC2 has been shown to suppress the differentiation of mesenchymal stem cells (MSCs) into myocytes and adipocytes. In the present study, we examined the role of DEC2 in the chondrogenic differentiation of human MSCs. The overexpression of DEC2 exerted minimal effects on the proliferation of MSCs in monolayer cultures with the growth medium under undifferentiating conditions, whereas it suppressed increases in DNA content, glycosaminoglycan content, and the expression of several chondrocyte-related genes, including aggrecan and type X collagen alpha 1, in MSC pellets in centrifuge tubes under chondrogenic conditions. In the pellets exposed to chondrogenesis induction medium, DEC2 overexpression downregulated the mRNA expression of fibroblast growth factor 18, which is involved in the proliferation and differentiation of chondrocytes, and upregulated the expression of p16INK4, which is a cell cycle inhibitor. These findings suggest that DEC2 is a negative regulator of the proliferation and differentiation of chondrocyte lineage-committed mesenchymal cells.
authors.affiliation: Department of Orthodontic Medicine, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sasamoto
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Kanawa
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Takeuchi
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Harada
authors.affiliation: Department of Pediatric Dentistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Goto
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Noshiro
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Ketut
authors.initials: K
authors.lastname: Suardita
authors.affiliation: Department of Orthodontic Medicine, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanne
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
mesh_terms: D053674:Aggrecans / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024121:Collagen Type X / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics; D005786:Gene Expression Regulation; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053674:Aggrecans; D051792:Basic Helix-Loop-Helix Proteins; D024121:Collagen Type X; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA; D005346:Fibroblast Growth Factors; D006025:Glycosaminoglycans; C422085:BHLHE41 protein, human; C113569:fibroblast growth factor 18