Histone Deacetylase 3 Depletion in Osteo/Chondroprogenitor Cells Decreases Bone Density and Increases Marrow Fat

Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health

The impact of minority ethnic businesses on the spatial character of London’s high streets

Research shows that a variety of building types, sizes and street morphologies can support a diversified mix of uses and thus contribute to the vitality of town centres. Other studies have highlighted the special role of minority ethnic businesses in this context. This study set out to examine the relationship between spatial accessibility, commercial diversity (as a measure of land use mixing) and minority ethnic business (MEB) diversity in ten of London’s high streets. We found that streets with a significant MEB presence were more likely to benefit from commercial diversity and that the sampled MEB units were measurably smaller in size. We also found the location of larger clusters of MEB businesses to be more accessible, both locally and across the city. The study also found three distinct types of MEB centres: ranging from high streets with a small MEB presence, others with a high rate of MEB mixing, and a third type: the ‘ethnic marketplace’, with a singular ethnic character. We conclude that greater attention should be given to designing street accessibility, lot configuration, mixed building sizes, and land use mixing, so as to serve the long-term economic and social vitality of local town centres