{"id":"06859e8d-c6d4-5361-a5e0-06d236e65c10","stable_key":"1ff3a29f-ef80-5bff-9300-30b98c60b90d:strontium-calcimimetic-dissociation","predicate":"does_not_reproduce","statement":"AC-265347 and BTU-compound 13 potentiated calcium/strontium CaSR signaling in HEK293 cells but neither replicated nor potentiated strontium inhibition of human osteoclast function.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"70acd523-de49-57ba-9a23-5230da14dab9","mechanism_event_label":"A stronger receptor assay signal did not guarantee the same cell-level outcome.","subject":{"id":"394445e9-6d9e-58f0-b5d6-e04b4d767710","slug":"casr-calcimimetic-ac265347-btu13","display_name":"AC-265347 and BTU-compound 13 CaSR modulators","entity_type_key":"cellular_process"},"object":{"id":"1546b799-1a34-5d1b-a54d-01c0d364bc86","slug":"human-strontium-osteoclast-function","display_name":"Maturation, TRAP activity and resorption in human osteoclast cultures","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"70acd523-de49-57ba-9a23-5230da14dab9","stable_key":"1ff3a29f-ef80-5bff-9300-30b98c60b90d:strontium-calcimimetic-dissociation-event","event_type":"observed_relationship","label":"A stronger receptor assay signal did not guarantee the same cell-level outcome.","description":"AC-265347 and BTU-compound 13 potentiated calcium/strontium CaSR signaling in HEK293 cells but neither replicated nor potentiated strontium inhibition of human osteoclast function.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"394445e9-6d9e-58f0-b5d6-e04b4d767710","slug":"casr-calcimimetic-ac265347-btu13","display_name":"AC-265347 and BTU-compound 13 CaSR modulators","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1546b799-1a34-5d1b-a54d-01c0d364bc86","slug":"human-strontium-osteoclast-function","display_name":"Maturation, TRAP activity and resorption in human osteoclast cultures","entity_type_key":"cellular_process"},"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":"1c0d5c58-d358-5501-9bdf-8999bcf79fd4","slug":"casr","display_name":"Calcium-sensing receptor / CaSR","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"97607549-3a37-544e-b6e6-266887f7c35f","slug":"strontium-ion","display_name":"Strontium ion / Sr2+","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Paired receptor and human osteoclast experiments; cinacalcet behaved differently.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Distinct ligand and cell contexts; no claim that CaSR alone fully explains osteoclast effects.","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":"plain_language","value_text":"A stronger receptor assay signal did not guarantee the same cell-level outcome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Divergent effects of strontium and calcium-sensing receptor positive allosteric modulators (calcimimetics) on human osteoclast activity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29714810/ · DOI 10.1111/bph.14344","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b9aee8ec-04ff-517e-8ac4-b265c2900be8","evidence_kind":"source_excerpt","locator":"Lines 262-268","start_line":262,"end_line":268,"excerpt":"## strontium-calcimimetic-dissociation\nA stronger receptor assay signal did not guarantee the same cell-level outcome.\nAC-265347 and BTU-compound 13 potentiated calcium/strontium CaSR signaling in HEK293 cells but neither replicated nor potentiated strontium inhibition of human osteoclast function.\nModel: Paired receptor and human osteoclast experiments; 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