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Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels of such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP‐2) is of tremendous interest for bone regenerative medicine, osteoporosis therapeutics, and beyond. Here, contribution of BMP‐2 signaling and extracellular mechanical cues to the osteogenic commitment of C2C12 cells is investigated. It is revealed that these two distinct pathways are integrated at the transcriptional level to provide multifactorial control of cell differentiation. The activation of osteogenic genes requires the cooperation of BMP‐2 pathway‐associated Smad1/5/8 heteromeric complexes and mechanosensitive YAP/TAZ translocation. It is further demonstrated that the Smad complexes remain bound onto and active on target genes, even after BMP‐2 removal, suggesting that they act as a "molecular memory unit." Thus, synergistic stimulation with BMP‐2 and mechanical cues drives osteogenic differentiation in a programmable fashion. [ABSTRACT FROM AUTHOR]

Vitamin D (Vit D) by means of its biological active form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), has a protective effect on the skeleton by acting on calcium homeostasis and bone formation. Furthermore, Vit D has a direct effect on mesenchymal stem cells (MSCs) in stimulating their osteogenic differentiation. In this work, we present for the first time the effect of 1,25(OH)2D3 on MSC adhesion. Considering that cell adhesion to the substrate is fundamental for cell commitment and differentiation, we focused on the expression of αVβ3 integrin, which has a key role in the commitment of MSCs to the osteoblastic lineage. Our data indicate that Vit D increases αVβ3 integrin expression inducing the formation of focal adhesions (FAs). Moreover, we assayed MSC commitment in the presence of the extracellular matrix (ECM) glycoprotein fibronectin (FN), which is able to favor cell adhesion on surfaces and also to induce osteopontin (OPN) expression: this suggests that Vit D and FN synergize in supporting cell adhesion. Taken together, our findings provide evidence that Vit D can promote osteogenic differentiation of MSCs through the modulation of αVβ3 integrin expression and its subcellular organization, thus favoring binding with the matrix protein (FN). [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have been identified in human dental tissues. Dental pulp stem cells (DPSCs) were classified within MSC family, are multipotent, can be isolated from adult teeth, and have been shown to differentiate, under particular conditions, into various cell types including osteoblasts. In this work, we investigated how the differentiation process of DPSCs toward osteoblasts is controlled. Recent literature data attributed to the nuclear receptor related 1 (NURR1), a still unclarified role in osteoblast differentiation, while NURR1 is primarily involved in dopaminergic neuron differentiation and activity. Thus, in order to verify if NURR1 had a role in DPSC osteoblastic differentiation, we silenced it during all the processes and compared the expression of the main osteoblastic markers with control cultures. Our results showed that the inhibition of NURR1 significantly increased the expression of osteoblast markers collagen I and alkaline phosphatase. Further, in long time cultures, the mineral matrix deposition was strongly enhanced in NURR1-silenced cultures. These results suggest that NURR1 plays a key role in switching DPSC differentiation toward osteoblasts rather than neuronal or even other cell lines. In conclusion, DPSCs represent a source of osteoblast-like cells and downregulation of NURR1 strongly prompted their differentiation toward the osteoblastogenesis process. [ABSTRACT FROM AUTHOR]

Mesenchymal Stem Cells (MSCs) are multipotent cells able to differentiate into specialized cells developing from mesoderm and to regenerate different tissues [[1]]. Lorenzo Lo Muzio Marco Mascitti Marcella La Noce Francesca Posa Yasusei Kudo Nicola Cirillo REFERENCES 1 Dimarino A. M., Caplan A. I., Bonfield T. L. Mesenchymal stem cells in tissue repair. Interestingly, L. Li et al. have demonstrated the ability of the microporous composites, developed combining OPF/BP with SDF-1 I i , in promoting migration and osteogenic differentiation of rat bone marrow MSCs (BMSCs), which makes it a good material useful to increase bone regeneration. [Extracted from the article]

1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D (Vit D), increases intestinal absorption of calcium and phosphate, maintaining a correct balance of bone remodeling. Vit D has an anabolic effect on the skeletal system and is key in promoting osteoblastic differentiation of human Mesenchymal Stem Cells (hMSCs) from bone marrow. MSCs can be also isolated from the immature form of the tooth, the dental bud: Dental Bud Stem Cells (DBSCs) are adult stem cells that can effectively undergo osteoblastic differentiation. In this work we investigated the effect of Vit D on DBSCs differentiation into osteoblasts. Our data demonstrate that DBSCs, cultured in an opportune osteogenic medium, differentiate into osteoblast-like cells; Vit D treatment stimulates their osteoblastic features, increasing the expression of typical markers of osteoblastogenesis like RUNX2 and Collagen I (Coll I) and, in a more important way, determining a higher production of mineralized matrix nodules. [ABSTRACT FROM AUTHOR]