BMP signaling orchestrates a transcriptional network to control the fate of mesenchymal stem cells in mice.

Signaling pathways are used reiteratively in different developmental processes yet produce distinct cell fates through specific downstream transcription factors. In this study, we used tooth root development as a model with which to investigate how the BMP signaling pathway regulates transcriptional complexes to direct the fate determination of multipotent mesenchymal stem cells (MSCs). We first identified the MSC population supporting mouse molar root growth as Gli1+ cells. Using a Gli1-driven Cre-mediated recombination system, our results provide the first in vivo evidence that BMP signaling activity is required for the odontogenic differentiation of MSCs. Specifically, we identified the transcription factors Pax9, Klf4, Satb2 and Lhx8 as being downstream of BMP signaling and expressed in a spatially restricted pattern that is potentially involved in determining distinct cellular identities within the dental mesenchyme. Finally, we found that overactivation of one key transcription factor, Klf4, which is associated with the odontogenic region, promotes odontogenic differentiation of MSCs. Collectively, our results demonstrate the functional significance of BMP signaling in regulating MSC fate during root development and shed light on how BMP signaling can achieve functional specificity in regulating diverse organ development.

Molecular and biotechnological advances in milk proteins in relation to human health.

Milk and colostrum is a rich source of proteins/peptides which have crucial roles in both neonates and adults. Milk bioactive proteins and peptides are potential health-enhancing nutraceuticals for food. Many bioactive peptides/proteins may be used as nutraceuticals, for example, in the treatment of cancer, asthma, diarrhea, hypertension, thrombosis, dental diseases, as well as mineral malabsorption, and immunodeficiency. The following components of milk are of particular interest in the recent years: 1) Lactoferrin [Lf] has antibacterial, antifungal, antiviral, antiparasite and antitumor activities and accelerates immunomodulatory properties. Lf is a potent inhibitor for several enveloped and naked viruses, such as rotavirus, enterovirus and adenovirus. Lf is resistant to tryptic digestion and breast-fed infants excrete high levels of faecal Lf, so that its effect on viruses replicating in the gastrointestinal tract is of great interest. 2) Casein has been protective in experimental bacteremia by eliciting myelopoiesis. Casein hydrolyzates were also protective in diabetic animals, reduced the tumor growth and diminished colicky symptoms in infants. 3) A Proline rich polypeptide [PRP] revealed variety of immunotropic functions, including promotion of T-cell activation and inhibition of autoimmune disorders such as multiple sclerosis. 4) alpha-Lactalbumin [LA] demonstrates antiviral, antitumor and anti-stress properties. 5) Lactoperoxidase shows antibacterial properties. 6) Lysozyme is effective in treatment of periodentitis and prevention of tooth decay. Taken together, milk-derived proteins and peptides are bio-available and safe for the prevention and treatment of various disorders in humans and may play a complementary [natural agents] rather than a substitutional role to the toxic synthetic pharmacological drugs.