title: A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells.
abstract: Pluripotent mesenchymal stem cells (MSCs) are bone marrow stromal progenitor cells that can differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. Several signaling pathways have been shown to regulate the lineage commitment and terminal differentiation of MSCs. Here, we conducted a comprehensive analysis of the 14 types of bone morphogenetic protein (BMPs) for their abilities to regulate multilineage specific differentiation of MSCs. We found that most BMPs exhibited distinct abilities to regulate the expression of Runx2, Sox9, MyoD, and PPARgamma2. Further analysis indicated that BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 effectively induced both adipogenic and osteogenic differentiation in vitro and in vivo. BMP-induced commitment to osteogenic or adipogenic lineage was shown to be mutually exclusive. Overexpression of Runx2 enhanced BMP-induced osteogenic differentiation, whereas knockdown of Runx2 expression diminished BMP-induced bone formation with a decrease in adipocyte accumulation in vivo. Interestingly, overexpression of PPARgamma2 not only promoted adipogenic differentiation, but also enhanced osteogenic differentiation upon BMP-2, BMP-6, and BMP-9 stimulation. Conversely, MSCs with PPARgamma2 knockdown or mouse embryonic fibroblasts derived from PPARgamma2(-/-) mice exhibited a marked decrease in adipogenic differentiation, coupled with reduced osteogenic differentiation and diminished mineralization upon BMP-9 stimulation, suggesting that PPARgamma2 may play a role in BMP-induced osteogenic and adipogenic differentiation. Thus, it is important to understand the molecular mechanism behind BMP-regulated lineage divergence during MSC differentiation, as this knowledge could help us to understand the pathogenesis of skeletal diseases and may lead to the development of strategies for regenerative medicine.
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, and The Children's Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Kang
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Song
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.forename: Ni
authors.initials: N
authors.lastname: Tang
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Luo
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Bi
authors.forename: Bai-Cheng
authors.initials: BC
authors.lastname: He
authors.forename: Jong Kyung
authors.initials: JK
authors.lastname: Park
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.forename: Jiayi
authors.initials: J
authors.lastname: Huang
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Su
authors.forename: Gao-Hui
authors.initials: GH
authors.lastname: Zhu
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.forename: Hong
authors.initials: H
authors.lastname: Yin
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Zuo
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Pan
authors.forename: Jikun
authors.initials: J
authors.lastname: Shen
authors.forename: Tamara
authors.initials: T
authors.lastname: Vokes
authors.forename: Russell R
authors.initials: RR
authors.lastname: Reid
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D010012:Osteogenesis / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation
chemical_list: D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D047495:PPAR gamma; D020033:Protein Isoforms; C493716:Runx2 protein, mouse