Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones

Yuko Katoh-Fukui; Takashi Baba; Tetsuya Sato; Hiroyuki Otake; Yuko Nagakui-Noguchi; Miyuki Shindo; Mikita Suyama; Yasuyuki Ohkawa; Hideki Tsumura; Ken-Ichirou Morohashi; Maki Fukami

doi:10.1016/j.bone.2018.10.021

Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones

Bone. 2019 Mar:120:219-231. doi: 10.1016/j.bone.2018.10.021. Epub 2018 Oct 30.

Authors

Affiliations

¹ Department of Molecular Endocrinology, National Research Institute of Child Health and Development, Tokyo 157-8535, Japan. Electronic address: fukui-y@ncchd.go.jp.
² Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.
³ Department of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan; Division of Bioinformatics, Kyushu University, Fukuoka, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Fukuoka, Japan.
⁴ Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁵ The National Center for Geriatrics and Gerontology, Aichi, Japan.
⁶ Department of Experimental Animals, National Research Institute of Child Health and Development, Tokyo, Japan.
⁷ Department of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Fukuoka, Japan; Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
⁸ Department of Molecular Endocrinology, National Research Institute of Child Health and Development, Tokyo 157-8535, Japan.

PMID: 30389610
DOI: 10.1016/j.bone.2018.10.021

Abstract

A set of key developmental genes is essential for skeletal growth from multipotent progenitor cells at weaning. Polycomb group proteins, which regulate such genes contributes to the cell lineage commitment and subsequent differentiation via epigenetic chromatin modification and remodeling. However, it is unclear which cell lineage and gene sets are targeted by polycomb proteins during skeletal growth. We now report that mice deficient in a polycomb group gene Cbx2^cterm/cterm exhibited skeletal hypoplasia in the tibia, femur, and cranium. Long bone cavities in these mice contained fewer multipotent mesenchymal stromal cells. RNA-sequencing of bone marrow cells showed downregulation and upregulation of osteoblastic and adipogenic genes, respectively. Furthermore, the expression levels of genes specifically expressed in B-cell precursors were decreased. Forced expression of Cbx2 in Cbx2^cterm/cterm bone marrow stromal cell recovered fibroblastic colony formation and suppressed adipogenic differentiation. Collectively, our results suggest that Cbx2 controls the maintenance and adipogenic differentiation of mesenchymal stromal cells in the bone marrow.

Keywords: Adipocyte; Bone marrow; Growth; Polycomb.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipogenesis*
Animals
Animals, Newborn
Bone and Bones / cytology*
Femur / abnormalities
Gene Expression Regulation
Growth Plate / abnormalities
Mesenchymal Stem Cells / metabolism
Mice, Inbred C57BL
Osteoblasts / cytology*
Osteoblasts / metabolism*
Polycomb Repressive Complex 1 / genetics*
Polycomb Repressive Complex 1 / metabolism
Tibia / abnormalities

Substances

Cbx2 protein, mouse
Polycomb Repressive Complex 1