Abstract
In the well-known superfamily of transforming growth factors beta (TGF-b), bone morphogenetic proteins (BMPs) are one of the most compelling cytokines for their major role in regulation of cell growth and differentiation in both embryonic and adult tissues. This subfamily was first described for its ability of potentiating bone formation, but nowadays, the power of BMPs is well beyond the bone healing scope. Some of the BMPs have been well studied and described in the literature, but the BMP9 is still worthy of attention. It has been shown by many authors that it is the most potent osteogenic BMP. Moreover, it has been described as one of the rare circulating BMPs. In this paper, we will review the recent literature on BMP9 and the different avenues for future research in that field. Our primary scope is to review its relation to bone formation and to elaborate on the available literature on other systems.
Highlights
Fifty years ago, Urist et al first reported that demineralized bone matrix could promote ectopic bone formation by stimulating transformation of primitive mesenchymal cells of soft tissues into osteogenic cells [1]
The osteogenic potential of BMP9 was first studied through gene therapy, but nowadays it is used through its recombinant human form, recombinant human BMP9 (rhBMP9)
The study of BMP9 bone formation has led to a better understanding on endochondral bone healing, and of the new insights in delivery systems that can enhance its effect as well as improved comprehension of the traumatic heterotopic ossification (HO) and its relation to BMP9
Summary
Urist et al first reported that demineralized bone matrix could promote ectopic bone formation by stimulating transformation of primitive mesenchymal cells of soft tissues into osteogenic cells [1]. BMP2/4/6/7/9 have been identified as having osteogenic properties, notably for their involvement in the regulation of osteoblast differentiation [12,13,14,15,16] and bone formation [14,17]. The osteogenic pathways including the Smad and different mediators of BMP9 were reviewed They point out crosstalk with other factors such as TGF-β1, Wnt/β-catenin signaling, Growth hormone, Mitogen activated protein kinases (MAPKs), Hypoxia inducible factor 1 alpha (HIF1α), Notch, Peroxisome proliferator-activated receptor gamma (PPAR-γ), insulin-like growth factor (IGF) and retinoid acid [27]. The compelling osteogenic potential of BMP9 will be discussed, and its role bone resorption, chondrogenesis, cancer development, angiogenesis, neurogenesis, hepatocyte physiology, glucose metabolism, and myogenesis (Figure 1)
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