The family of bone morphogenetic proteins (BMPs) comprises approximately 30 secreted cytokines that signal through transmembrane serine/threonine kinase receptors. The BMP signaling pathways are fine-tuned on multiple levels: Extracellular antagonists modify ligand activity; several co-receptors enhance or inhibit downstream signaling events through multiple mechanisms; and intracellular molecules further regulate the signaling outcome and mediate crosstalk with other pathways. BMPs affect structures and processes throughout the entire body, ranging from embryonic patterning and development through stem cells and their niches, to tissue homeostasis and regeneration. This comprehensive involvement in various tissues had not been expected by Marshall Urist, who initially discovered the ability of an unknown factor in bone to induce bone growth in muscle and subsequently suggested the name "bone morphogenetic protein." Today, recombinant BMPs are used in clinical practice for the treatment of bone and kidney disorders, and new genetically modified BMPs are emerging as promising tools in regenerative medicine and tissue engineering. Clearly, the functions of BMPs within the body are more versatile than initially suspected. To discuss modern trends in BMP signaling, leaders in the field met for the First International BMP Workshop in Berlin in September 2009. Here, we summarize new insights on the roles of BMPs in various tissues and highlight recent findings in cell, structural, and developmental biology as well as the therapeutic potential of BMPs. Finally, we conclude that BMPs today deserve to be called body morphogenetic proteins.
Bone is specific to vertebrates, and originated as mineralization around the basal membrane of the throat or skin, giving rise to tooth-like structures and protective shields in animals with a soft cartilage-like endoskeleton. A combination of fossil anatomy and genetic information from modern species has improved our understanding of the evolution of bone. Thus, even in man, there are still similarities in the molecular regulation of skin appendages and bone. This article gives a brief overview of the major milestones in skeletal evolution. Some molecular machineries involving members of core genetic networks and their interactions are described in the context of both old theories and modern genetic approaches.
Epigenetic changes refer to modifications caused by heritable but potentially reversible changes in gene expression not coded in the DNA sequence. Evidence has been provided that various environmental factors and dietary bioactive compounds contribute to cancer development through epigenetic mechanisms. The main mechanisms of epigenetic control in mammals are DNA methylation, histone modifications, and RNA silencing through noncoding RNAs. The inhibition of DNA methyltransferases (DNMTs) involved in DNA methylation of CpG-rich regions of gene promoters and various enzymes involved in the chromatin condensation such as histone deacetylases (HDACs) have been recognized as potent strategies for cancer therapy and chemoprevention. Treatments using natural compounds such as green tea polyphenols, soy isoflavones, curcumin, resveratrol, isothiocyanates, and butyrate (an intestinal product from dietary fiber) modulate DNMT or HDAC gene expression and/or protein levels and activities, indicating that natural compounds could have strong potential to reverse epigenetic changes, without the adverse toxic effects associated with synthetic epigenetic inhibitors used in chemotherapy. Further characterization of the chemopreventive properties of various dietary bioactive compounds is warranted to potentially establish the clinical utility of dietary factors as anticancer compounds either alone or in combination with other dietary factors or clinically relevant therapeutics. Moreover, these characterizations are useful for personalized dietary recommendations and chemopreventive strategies for reducing cancer incidence.
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