title: BMP9 signaling in stem cell differentiation and osteogenesis.
abstract: Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily and play a critical role in skeletal development, bone formation and stem cell differentiation. Disruptions in BMP signaling result in a variety of skeletal and extraskeletal anomalies. BMP9 is a poorly characterized member of the BMP family and is among the most osteogenic BMPs, promoting osteoblastic differentiation of mesenchymal stem cells (MSCs) both in vitro and in vivo. Recent findings from various in vivo and molecular studies strongly suggest that the mechanisms governing BMP9-mediated osteoinduction differ from other osteogenic BMPs. Many signaling pathways with diverse functions have been found to play a role in BMP9-mediated osteogenesis. Several of these pathways are also critical in the differentiation of other cell lineages, including adipocytes and chondrocytes. While BMP9 is known to be a potent osteogenic factor, it also influences several other pathways including cancer development, angiogenesis and myogenesis. Although BMP9 has been demonstrated as one of the most osteogenic BMPs, relatively little is known about the specific mechanisms responsible for these effects. BMP9 has demonstrated efficacy in promoting spinal fusion and bony non-union repair in animal models, demonstrating great translational promise. This review aims to summarize our current knowledge of BMP9-mediated osteogenesis by presenting recently completed work which may help us to further elucidate these pathways.
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center Chicago, IL 60637, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Lamplot
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Qin
authors.forename: Guoxin
authors.initials: G
authors.lastname: Nan
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Liangjun
authors.initials: L
authors.lastname: Yin
authors.forename: Justin
authors.initials: J
authors.lastname: Tomal
authors.forename: Ruidong
authors.initials: R
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Shui
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Kim
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.forename: Jiye
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Kong
authors.forename: Sahitya
authors.initials: S
authors.lastname: Denduluri
authors.forename: Mary Rose
authors.initials: MR
authors.lastname: Rogers
authors.forename: Abdullah
authors.initials: A
authors.lastname: Pratt
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.forename: Jovito
authors.initials: J
authors.lastname: Angeles
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Shi
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
keywords: BMP; BMP9; IGF; TGF-β; Wnt; bone regeneration; mesenchymal stem cells; osteogenesis; signal transduction