A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives.

Jonathan W Lowery,Brice Brookshire,Vicki Rosen

doi:10.1155/2016/7290686

Jonathan W Lowery, Brice Brookshire + Show 1 more

Open Access

https://doi.org/10.1155/2016/7290686

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Abstract

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-β family of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide-perspective on strategies that increase or decrease BMP signaling. We briefly outline the current FDA-approved approaches, highlight emerging next-generation technologies, and postulate prospective avenues for future investigation. We also detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF-β pathways.

Highlights

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-β family of ligands
Approximately thirty distinct human proteins are named BMPs and some have been assigned as Growth/Differentiation Factors (GDFs)
Proteins that participate in the activation of SMAD1/5/8, are bona fide components of the canonical BMP signaling cascade

Summary

Introduction

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-β family of ligands. Proteins that participate in the activation of SMAD1/5/8, are bona fide components of the canonical BMP signaling cascade On this basis, it is possible to identify approximately thirteen bone fide BMP ligands in humans. Depending on the stem cell population in question, BMP signaling may act in a contextspecific manner to either stimulate differentiation or promote maintenance of pluripotency. Aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies (reviewed in [13,14,15,16]) Concomitant with this increased clinical significance, there is a growing need to develop effective strategies that modulate BMP signaling as a means of regulating stem cell populations. We detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF-β pathways

Strategies to Activate the BMP Pathway

Strategies to Inhibit the BMP Pathway

Indirect Modulation of BMP Pathway Activity via Activating Other Pathways

Methods