Study summary · research use only
Gli1(+) progenitors mediate bone anabolic function of teriparatide via Hh and Igf signaling
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this mouse study, researchers examined the cellular targets of teriparatide, a widely used bone anabolic drug, focusing on Gli1-positive metaphyseal mesenchymal progenitors (MMPs), a source of osteoblasts in postnatal growing mice. Using lineage tracing, teriparatide was associated with increased proliferation and osteoblast differentiation of MMPs. Single-cell RNA sequencing identified heterogeneity among MMPs, including a chondrocyte-like osteoprogenitor (COP) subpopulation expressing the highest levels of Hedgehog (Hh) target genes and insulin-like growth factor 1 receptor (Igf1r); COP also expressed Pth1r and further upregulated Igf1r after teriparatide treatment. Inhibiting Hh signaling or deleting Igf1r from MMPs reduced the proliferative and osteogenic response to teriparatide. The authors identify COP as a teriparatide target in which Hh and Igf signaling contribute to the bone-forming response in growing mice.
Abstract
Teriparatide is the most widely prescribed bone anabolic drug in the world, but its cellular targets remain incompletely defined. The Gli1+ metaphyseal mesenchymal progenitors (MMPs) are a main source for osteoblasts in postnatal growing mice, but their potential response to teriparatide is unknown. Here, by lineage tracing, we show that teriparatide stimulates both proliferation and osteoblast differentiation of MMPs. Single-cell RNA sequencing reveals heterogeneity among MMPs, including an unexpected chondrocyte-like osteoprogenitor (COP). COP expresses the highest level of Hedgehog (Hh) target genes and the insulin-like growth factor 1 receptor (Igf1r) among all cell clusters. COP also expresses Pth1r and further upregulates Igf1r upon teriparatide treatment. Inhibition of Hh signaling or deletion of Igf1r from MMPs diminishes the proliferative and osteogenic effects of teriparatide. The study therefore identifies COP as a teriparatide target wherein Hh and insulin-like growth factor (Igf) signaling are critical for the osteoanabolic response in growing mice.
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