Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes

• DOI: 10.1073/pnas.0502249102
• Publication Date: 2005-06-24T00:38:58Z
• Authors: Yves Sabbagh; Thomas O. Carpenter; Marie B. Demay
• Keywords: Hypophosphatemia; PHEX; Osteomalacia; Hypophosphatemic Rickets

Rickets is seen in association with vitamin D deficiency and several genetic disorders associated abnormal mineral ion homeostasis. Studies receptor (VDR)-null mice have demonstrated that expansion of the late hypertrophic chondrocyte layer, characteristic rickets, secondary to impaired apoptosis these cells. The observation normalization homeostasis VDR-null prevents rachitic changes suggests rickets hypocalcemia, hypophosphatemia, or hyperparathyroidism, rather than VDR action. To determine which abnormalities responsible for subsequent changes, two additional models were examined: diet-induced hypophosphatemia/hypercalcemia hypophosphatemia mutations Phex gene. former model suppressed parathyroid hormone levels as a consequence hypercalcemia. latter demonstrates normal calcium levels, but 1,25-dihydroxyvitamin are inappropriately low degree hypophosphatemia. Our studies demonstrate phosphorus required growth plate maturation implicate critical role phosphate-regulated chondrocytes via activation caspase-9-mediated mitochondrial pathway.