Bone Morphogenetic Protein (BMP) signaling in development and human diseases

Abstract

Bone Morphogenetic Proteins (BMPs) are a group of signaling molecules that belongs to the Transforming Growth Factor-β (TGF-β) superfamily of proteins. Initially discovered for their ability to induce bone formation, BMPs are now known to play crucial roles in all organ systems. BMPs are important in embryogenesis and development, and also in maintenance of adult tissue homeostasis. Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects, highlighting the essential functions of BMPs. In this review, we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development. A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling.

Down-regulation of nestin in mesenchymal stem cells derived from peripheral blood through blocking bone morphogenesis pathway

“…BMP signaling is also important in mesoderm formation and cardiac development during embryogenesis. BMP4 has been demonstrated to display a major role in developmental stages including mesoderm differentiation (Wang et al 2014).…”

An Update of Bone Morphogenetic Proteins as Biomarker and Therapy for Cancer

“…Thus, dysregulation of such protein, which regulates embryogenesis or organogenesis may cause tumorigenesis and metastasis. Abnormal expressions of bone morphogenetic proteins (BMPs) which play critical role in embryogenesis, cartilage, and bone formation have been found in various types of cancers, which have been linked with tumorigenesis and metastasis of many cancer types [11][12][13][14][15]. However, the role of BMPs in tumorigenesis still remains a debate [16].…”

“…BMPs transduce intracellular signaling cascades by both canonical and non-canonical pathways [12,17]. In canonical pathway, BMPs transduce their signals by binding with serine/threonine protein kinase receptors, followed by forming heterotetrameric complex of receptor type 1 and 2.…”

“…In canonical pathway, BMPs transduce their signals by binding with serine/threonine protein kinase receptors, followed by forming heterotetrameric complex of receptor type 1 and 2. This heterotetrameric complex when activated upon phosphorylation, phosphorylates regulatory receptor substrates R-Smads (Smad1, Smad5 and Smad8), which binds to co-Smad, Smad4 which also transduces TGFβ signaling, and subsequently undergoes nuclear translocation and regulate gene transcription with aid of other coactivator/co-repressor [12,17]. All BMPs usually mediate their signaling cascade following this basic mechanism.…”

“…All BMPs usually mediate their signaling cascade following this basic mechanism. However, BMP-2 and BMP-4 first bind to receptor type I to make complex with receptor type II, whereas BMP-6 and BMP-7 first interact with type II to form complex by recruiting type I [12,18]. Therefore, these differences may generate distinct types of intracellular signaling.…”