Am J Stem Cell 2013;2(1):1-21

Review Article
BMP9 signaling in stem cell differentiation and osteogenesis

Joseph D Lamplot, Jiaqiang Qin, Guoxin Nan, Jinhua Wang, Xing Liu, Liangjun Yin, Justin Tomal, Ruidong Li, Wei Shui, Hongyu Zhang,
Stephanie H Kim, Wenwen Zhang, Jiye Zhang, Yuhan Kong, Sahitya Denduluri, Mary Rose Rogers, Abdullah Pratt, Rex C Haydon, Hue H
Luu, Jovito Angeles, Lewis L Shi, Tong-Chuan He

Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA;
Stem Cell Biology and Therapy Laboratory of the Key Laboratory for Pediatrics co-designated by Chinese Ministry of Education, The
Children’s Hos-pital of Chongqing Medical University, Chongqing 400014, China; The Affiliated Hospitals and the Key Laboratory of
Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China;
Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences and the Affiliated Hospital of Stomatology, Chongqing Medical
University, Chongqing 401147, China

Received December 13, 2012; Accepted January 23, 2013; Epub March 8, 2013; Published March 18, 2013

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. (AJSC1212001).

Keywords: BMP, BMP9, bone regeneration, IGF, osteogenesis, TGF-β, Wnt, signal transduction, mesenchymal stem cells

Address correspondence to: Dr. Tong-Chuan He, Molecular Oncology Laboratory, The University of Chicago Medical Center, 5841 South
Maryland Avenue, MC 3079, Chicago, IL 60637, USA. Tel: 773-702-7169; Fax: 773-834-4598; E-mail:
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