59 research outputs found
Bone remodelling: A signalling system for osteoclast regulation
No full textAbstractTwo physiological regulators of osteoclast maturation have recently been identified: the secreted protein osteoprotegerin and the cell-surface ligand to which it binds. These proteins are likely to play an important part in the control of bone resorption, but are also likely to have important roles in other tissues
Induction of Myogenesis in Mesenchymal Cells by MyoD Depends on Their Degree of Differentiation
No full textAbstractExpression of a transfected MyoD gene induces myogenic differentiation of most cell types. In this study, we evaluated the ability of an exogenous MyoD gene to induce myogenic conversion in two pairs of matched cell lines with different degrees of differentiation within either the osteoblastic or chondrocytic lineage. We show that osteoblasts and chondrocytes are resistant to the myogenic effects of MyoD alone. However, in their less-differentiated cell line counterparts, MyoD induces expression of muscle-cell-specific markers. Less-differentiated osteoblasts can be made resistant to MyoD-induced myogenic conversion by induction of adipogenic differentiation using dexamethasone. Finally, a dominant positive form of MyoD, one which is tethered to a partner, E47, activates muscle-specific gene expression in osteoblasts. Our results suggest that the response of a cell to MyoD depends on its lineage and its degree of differentiation. Furthermore, commitment of cells to the osteoblastic or chondrocytic lineage may involve inhibition of alternative pathways, such as those leading to myoblastic differentiation. Finally, osteoblasts may express a protein(s) which interferes with the activity of MyoD by inhibiting its association with E proteins. This interference can be overcome by expression of the MyoD–E47 hybrid, suggesting that osteoblasts are otherwise competent to undergo myogenic conversion
Author Correction: Shallow shotgun sequencing reduces technical variation in microbiome analysis
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Shallow shotgun sequencing reduces technical variation in microbiome analysis
No full textAbstract The microbiome is known to play a role in many human diseases, but identifying key microbes and their functions generally requires large studies due to the vast number of species and genes, and the high levels of intra-individual and inter-individual variation. 16S amplicon sequencing of the rRNA gene is commonly used for large studies due to its comparatively low sequencing cost, but it has poor taxonomic and functional resolution. Deep shotgun sequencing is a more accurate and comprehensive alternative for small studies, but can be cost-prohibitive for biomarker discovery in large populations. Shallow or moderate-depth shotgun metagenomics may serve as a viable alternative to 16S sequencing for large-scale and/or dense longitudinal studies, but only if resolution and reproducibility are comparable. Here we applied both 16S and shallow shotgun stool microbiome sequencing to a cohort of 5 subjects sampled twice daily and weekly, with technical replication at the DNA extraction and the library preparation/sequencing steps, for a total of 80 16S samples and 80 shallow shotgun sequencing samples. We found that shallow shotgun sequencing produced lower technical variation and higher taxonomic resolution than 16S sequencing, at a much lower cost than deep shotgun sequencing. These findings suggest that shallow shotgun sequencing provides a more specific and more reproducible alternative to 16S sequencing for large-scale microbiome studies where costs prohibit deep shotgun sequencing and where bacterial species are expected to have good coverage in whole-genome reference databases
Inhibition of TGF-β receptor signaling in osteoblasts leads to decreased bone remodeling and increased trabecular bone mass
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