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    Circulating αKlotho influences phosphate handling by controlling FGF23 production

    The goal of this study was to test whether circulating αKlotho (cKL), which is a cleavage product of membrane-bound Klotho, regulates phosphate handling by influencing FGF23 expression.  Mice, treated with an adeno-associated virus expressing cKL, exhibited dose-dependent hypophosphatemia and hypocalcemia, with markedly elevated FGF23. These animals also manifested fractures, reduced bone mineral content, expanded growth plates, and severe osteomalacia, with highly increased bone Fgf23 mRNA (>150 fold).

    Smith RC, O’Bryan LM, Farrow EG, Summers LJ, Clinkenbeard EL, Roberts JL, et al.