title: Role of MSX1 in Osteogenic Differentiation of Human Dental Pulp Stem Cells.
abstract: Msh homeobox 1 (MSX1) encodes a transcription factor implicated in embryonic development of limbs and craniofacial tissues including bone and teeth. Although MSX1 regulates osteoblast differentiation in the cranial bone of young animal, little is known about the contribution of MSX1 to the osteogenic potential of human cells. In the present study, we investigate the role of MSX1 in osteogenic differentiation of human dental pulp stem cells isolated from deciduous teeth. When these cells were exposed to osteogenesis-induction medium, runt-related transcription factor-2 (RUNX2), bone morphogenetic protein-2 (BMP2), alkaline phosphatase (ALPL), and osteocalcin (OCN) mRNA levels, as well as alkaline phosphatase activity, increased on days 4-12, and thereafter the matrix was calcified on day 14. However, knockdown of MSX1 with small interfering RNA abolished the induction of the osteoblast-related gene expression, alkaline phosphatase activity, and calcification. Interestingly, DNA microarray and PCR analyses revealed that MSX1 knockdown induced the sterol regulatory element-binding protein 2 (SREBP2) transcriptional factor and its downstream target genes in the cholesterol synthesis pathway. Inhibition of cholesterol synthesis enhances osteoblast differentiation of various mesenchymal cells. Thus, MSX1 may downregulate the cholesterol synthesis-related genes to ensure osteoblast differentiation of human dental pulp stem cells.
authors.affiliation: Department of Pediatric Dentistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Noriko
authors.identifier: 0000-0003-3574-6868
authors.initials: N
authors.lastname: Goto
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan; Department of Molecular Biology and Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Katsumi
authors.identifier: 0000-0001-8961-3134
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Dental Science for Health Promotion, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ida-Yonemochi
authors.affiliation: Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
authors.forename: Hayato
authors.identifier: 0000-0001-8571-9900
authors.initials: H
authors.lastname: Ohshima
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan; Department of Molecular Biology and Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Takeshi
authors.identifier: 0000-0003-3337-1775
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan; Department of Molecular Biology and Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Noshiro
authors.affiliation: Department of Molecular Biology and Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Chisa
authors.initials: C
authors.lastname: Shukunami
authors.affiliation: Department of Pediatric Dentistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kozai
authors.affiliation: Department of Dental and Medical Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Yukio
authors.identifier: 0000-0003-3182-3168
authors.initials: Y
authors.lastname: Kato