{"id":"09d3bc04-84a3-5a3d-a10a-e6c46e820a26","stable_key":"1ff3a29f-ef80-5bff-9300-30b98c60b90d:strontium-calcineurin-block","predicate":"inhibition_prevents","statement":"Cyclosporin A or FK506 blocked ranelate-associated NFATc1 activation and blunted osteoblast replication and phenotypic gene expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"5fe6d075-45d8-5f94-993f-5f7cc648fe28","mechanism_event_label":"Blocking the activating phosphatase interrupts the downstream response.","subject":{"id":"4c1eda36-bce1-580b-b308-7cdff624f780","slug":"mouse-calcineurin","display_name":"Mouse calcineurin phosphatase complex","entity_type_key":"protein_complex"},"object":{"id":"b4a1bee0-582b-5c47-817f-04b6764cfbe8","slug":"mouse-nfatc1","display_name":"Mouse NFATc1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"5fe6d075-45d8-5f94-993f-5f7cc648fe28","stable_key":"1ff3a29f-ef80-5bff-9300-30b98c60b90d:strontium-calcineurin-block-event","event_type":"observed_relationship","label":"Blocking the activating phosphatase interrupts the downstream response.","description":"Cyclosporin A or FK506 blocked ranelate-associated NFATc1 activation and blunted osteoblast replication and phenotypic gene expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4c1eda36-bce1-580b-b308-7cdff624f780","slug":"mouse-calcineurin","display_name":"Mouse calcineurin phosphatase complex","entity_type_key":"protein_complex"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b4a1bee0-582b-5c47-817f-04b6764cfbe8","slug":"mouse-nfatc1","display_name":"Mouse NFATc1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"2ca2864b-1ef0-54e4-8397-1dbe7207a0d2","slug":"strontium","display_name":"Strontium","entity_type_key":"nutrient_element"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a319eca8-b0ed-5a8c-8659-e7f106bed73a","slug":"strontium-ranelate","display_name":"Strontium ranelate","entity_type_key":"chemical_species"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Murine osteoblast inhibitor experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"These inhibitors have broader biological effects; not a clinical interaction estimate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"strontium","display_name":"Strontium","entity_type_key":"nutrient_element"}},{"dimension":"perturbation_agent","value_text":"inhibits","comparator":null,"unit":null,"notes":"Cyclosporin A or FK506 blocked ranelate-associated NFATc1 activation; the experiment used cyclosporin A as the calcineurin blocker. FK506 is the second agent and is not a ledger entity yet.","entity":{"slug":"cyclosporine-a","display_name":"Cyclosporine A / ciclosporin A","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Blocking the activating phosphatase interrupts the downstream response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Essential role of nuclear factor of activated T cells (NFAT)-mediated Wnt signaling in osteoblast differentiation induced by strontium ranelate. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20554534/ · DOI 10.1074/jbc.M110.110502","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"826e22aa-dc10-5aca-9c87-3bf721adc45d","evidence_kind":"source_excerpt","locator":"Lines 126-132","start_line":126,"end_line":132,"excerpt":"## strontium-calcineurin-block\nBlocking the activating phosphatase interrupts the downstream response.\nCyclosporin A or FK506 blocked ranelate-associated NFATc1 activation and blunted osteoblast replication and phenotypic gene expression.\nModel: Murine osteoblast inhibitor experiments.\nLimitations: These inhibitors have broader biological effects; not a clinical interaction estimate.\nEvidence access: Primary abstract\nEssential role of nuclear factor of activated T cells (NFAT)-mediated Wnt signaling in osteoblast differentiation induced by strontium ranelate. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20554534/ · DOI 10.1074/jbc.M110.110502","model_system":"Murine osteoblast inhibitor experiments.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"43ef0fe7-eb6c-5346-8381-f7694733b4dc","stable_key":"import-1ff3a29f-ef80-5bff-9300-30b98c60b90d","title":"Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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