Abstract
Bone morphogenetic proteins (BMPs) are a diverse class of growth factors that belong to the transforming growth factor-beta (TGFβ) superfamily. Although originally discovered to possess osteogenic properties, BMPs have since been identified as critical regulators of many biological processes, including cell-fate determination, cell proliferation, differentiation and morphogenesis, throughout the body. In the ocular lens, BMPs are important in orchestrating fundamental developmental processes such as induction of lens morphogenesis, and specialized differentiation of its fiber cells. Moreover, BMPs have been reported to facilitate regeneration of the lens, as well as abrogate pathological processes such as TGFβ-induced epithelial-mesenchymal transition (EMT) and apoptosis. In this review, we summarize recent insights in this topic and discuss the complexities of BMP-signaling including the role of individual BMP ligands, receptors, extracellular antagonists and cross-talk between canonical and non-canonical BMP-signaling cascades in the lens. By understanding the molecular mechanisms underlying BMP activity, we can advance their potential therapeutic role in cataract prevention and lens regeneration.
Highlights
Retinal ablation was correlated to shifting of the lens bow region posteriorly until the LECs completely surrounded the lens, highlighting the importance of the retina in providing positional lens fiber cell differentiation cues. In these mice, when fibroblast growth factor (FGF)-3 was overexpressed in lens, this rescued the loss of fiber cell differentiation, indicating that bone morphogenetic proteins (BMPs)-7 overexpression in the lens does not incapacitate the ability of LECs to respond to differentiation signals
We showed that exogenous administration of BMP-7 suppressed TGFβ2-induced epithelial-mesenchymal transition (EMT) by concurrent upregulation of pSmad1/5 and downregulation of pSmad2/3
Important advances have been made in elucidating the role of BMPs and BMP-signaling in the lens, it is clear from this review that there are still significant gaps in our understanding
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The activity of bone morphogenetic proteins (BMPs) was described by orthopedic surgeon, Marshall Urist in 1965 when he found that they could induce ectopic bone formation in rodents [1]; it was not until the late 1980s that the responsible BMP proteins were identified and characterized [2,3,4,5] Since their initial discovery, BMPs have been shown to exert pleiotropic effects on many tissues and processes beyond bone and osteogenesis, recognized as multifunctional proteins belonging to the transforming growth factor-beta (TGFβ) superfamily [6,7,8,9]. We discuss the importance of BMPs during the phases of lens development from the initial induction of the lens ectoderm in embryogenesis to later lens fiber differentiation processes We follow this with a discussion of the role of BMPs in promoting lens regeneration and in abrogating lens pathology, including its potential as a therapeutic for cataract prevention. We conclude by highlighting opportunities to fill the gaps in our current understanding of BMP-signaling in the lens and propose directions for future research
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