{"id":"0f0ce1f0-9c2a-5e6a-9c3c-fd6c6a0885b6","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vdm-phosphate-restriction-reduces-growth-plate-apoptosis","predicate":"low_availability_reduces","statement":"Diet-induced hypophosphatemic mice had impaired late hypertrophic-chondrocyte apoptosis and rachitic growth-plate expansion despite hypercalcemia and suppressed PTH.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"eb4b3822-305f-5c79-a2d0-9f2d52be6ff5","mechanism_event_label":"Low phosphate disrupted maturation of growth-plate cartilage even when calcium was high.","subject":{"id":"b28dfc54-a5ef-5f9e-ac1f-890b68e58dc3","slug":"inorganic-phosphate","display_name":"Inorganic phosphate","entity_type_key":"chemical_species"},"object":{"id":"97e6095f-d559-571e-a5e9-17fcd0ec49c2","slug":"hypertrophic-chondrocyte-apoptosis","display_name":"Hypertrophic chondrocyte apoptosis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"eb4b3822-305f-5c79-a2d0-9f2d52be6ff5","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vdm-phosphate-restriction-reduces-growth-plate-apoptosis-event","event_type":"biochemical_relationship","label":"Low phosphate disrupted maturation of growth-plate cartilage even when calcium was high.","description":"Diet-induced hypophosphatemic mice had impaired late hypertrophic-chondrocyte apoptosis and rachitic growth-plate expansion despite hypercalcemia and suppressed PTH.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b28dfc54-a5ef-5f9e-ac1f-890b68e58dc3","slug":"inorganic-phosphate","display_name":"Inorganic phosphate","entity_type_key":"chemical_species"},"role":"restricted-nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"elevated-circulating-mineral","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e162b0ab-1449-5471-b3c3-4638a0fa3a96","slug":"pth","display_name":"Parathyroid hormone / PTH","entity_type_key":"protein"},"role":"suppressed-hormone","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ac443e80-dc28-59d3-8be4-35abd67f06fd","slug":"hypertrophic-chondrocyte","display_name":"Hypertrophic chondrocyte","entity_type_key":"cell_type"},"role":"responsive-cell","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"97e6095f-d559-571e-a5e9-17fcd0ec49c2","slug":"hypertrophic-chondrocyte-apoptosis","display_name":"Hypertrophic chondrocyte apoptosis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"Vitamin D–calcium–phosphate regulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_locator","value_text":"Results: biochemical parameters, growth-plate histology and TUNEL; primary text excerpts cached in web-assay-excerpts.json","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_scope","value_text":"D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Wild-type mice fed high-calcium/low-phosphate diet; growth-plate histology and TUNEL assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"High-calcium/low-phosphate diet; biochemical comparisons at 24 days of age in Figure 2. Exact diet duration/formulation not resolved in retrieved passages.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The diet arm is separated from Vdr-null and Phex-mutant models. No single human serum threshold or claim that every rachitic disorder has one mechanism is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Vitamin D2 and D3","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"nutrient_topic","value_text":"Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Low phosphate disrupted maturation of growth-plate cartilage even when calcium was high.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[vdm-sabbagh2005] Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. 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No single human serum threshold or claim that every rachitic disorder has one mechanism is inferred.\nexposure: High-calcium/low-phosphate diet; biochemical comparisons at 24 days of age in Figure 2. Exact diet duration/formulation not resolved in retrieved passages.\ncross_nutrient: Vitamin D–calcium–phosphate regulation.\nevidence_locator: Results: biochemical parameters, growth-plate histology and TUNEL; primary text excerpts cached in web-assay-excerpts.json\nnutrient: Vitamin D2 and D3\nevidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.\n[vdm-sabbagh2005] Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. 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