SUMMARY
Nutritional supplementation with probiotics can prevent pathologic bone
loss. Here we examined the impact of supplementation with Lactobacillus
rhamnosus GG (LGG) on bone homeostasis in eugonadic young mice.
Micro-computed tomography revealed that LGG increased trabecular bone volume in
mice, which was due to increased bone formation. Butyrate produced in the gut
following LGG ingestion, or butyrate fed directly to germ-free mice, induced the
expansion of intestinal and bone marrow (BM) regulatory T (Treg) cells.
Interaction of BM CD8+ T cells with Treg cells resulted in increased
secretion of Wnt10b, a bone anabolic Wnt ligand. Mechanistically, Treg cells
promoted the assembly of a NFAT1-SMAD3 transcription complex in CD8+
cells, which drove expression of
Wnt10b−/−. Reducing Treg cell
numbers, or reconstitution of TCRβ−/− mice with
CD8+ T cells from
Wnt10b−/− mice, prevented
butyrate-induced bone formation and bone mass acquisition. Thus, butyrate
concentrations regulate bone anabolism via Treg cell-mediated regulation of
CD8+ T cell Wnt10b production.
Abstract. The reactive uptake of HOBr onto aqueous solutions containing CI' and Br-has been studied using a wetted-wall flow tube reactor. The uptake was found to be limited by
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