ArticlebioRxiv : the preprint server for biology2025
TGFβ signaling regulates the response of the skeleton to phosphate.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Inorganic phosphate (Pi) homeostasis is crucial to organismal health, yet the mechanisms underlying the regulation of it remain unclear. Critically, we lack a clear understanding of the Pi response circuitry in osteogenic cells that identifies altered serum Pi levels and transmits this information to changes in serum FGF23 levels, a key hormone regulating circulating Pi. We utilized genome-wide CRISPR screens in osteogenic Pi-responsive fluorescent reporter cell lines to identify regulators of the response to high phosphate, intersecting those results with loci associated with circulating FGF23 levels by genome-wide association studies (GWAS) and identified a potential role for TGF-β2. We found that each of the three ligands (TGF-β1, 2, 3) can enhance the response to Pi in osteogenic cell lines and ex vivo cultures of calvariae, while inhibitors of TGFβ receptor signaling dampen it. Co-treatment of Pi with TGFβ ligands led to an elevated, synergistic transcriptional induction of
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