{"id":"70173abf-9603-5b40-8b0c-754de4f74345","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-smad-runx2","predicate":"increases_phosphorylation","statement":"Orthosilicic acid increased phosphorylated SMAD1/5 and RUNX2 expression alongside osteogenic markers.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"31cd5a22-f538-519f-92d8-c0092ccb3c1d","mechanism_event_label":"The response extended to downstream bone-development regulators.","subject":{"id":"c497144d-1e90-5176-a475-2d715992f5b0","slug":"orthosilicic-acid","display_name":"Orthosilicic acid / Si(OH)4","entity_type_key":"small_molecule"},"object":{"id":"6c60fb69-a346-5608-938d-da09b08ff170","slug":"human-smad1-smad5","display_name":"Human SMAD1/SMAD5 signaling proteins","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"31cd5a22-f538-519f-92d8-c0092ccb3c1d","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-smad-runx2-event","event_type":"observed_relationship","label":"The response extended to downstream bone-development regulators.","description":"Orthosilicic acid increased phosphorylated SMAD1/5 and RUNX2 expression alongside osteogenic markers.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c497144d-1e90-5176-a475-2d715992f5b0","slug":"orthosilicic-acid","display_name":"Orthosilicic acid / Si(OH)4","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6c60fb69-a346-5608-938d-da09b08ff170","slug":"human-smad1-smad5","display_name":"Human SMAD1/SMAD5 signaling proteins","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"11b1cdb5-1b10-586b-9917-b4da18ac072f","slug":"silica","display_name":"Silica and soluble silicon","entity_type_key":"chemical_species"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a2b4dc1b-5982-501a-836a-00692b9fddea","slug":"human-bmp2","display_name":"Human BMP2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"30dd8e5f-7abe-5fd5-927d-e8204e5de6e5","slug":"runx2","display_name":"RUNX2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"091a1ec0-5867-5659-b199-b73a1ac8b9c6","slug":"human-type-i-collagen","display_name":"Human type I collagen","entity_type_key":"protein_complex"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"b043ce5c-8537-5099-8421-b07ec993dbde","slug":"bglap","display_name":"Osteocalcin / BGLAP","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human osteoblast-like cell lines, 10 micromolar exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Marker regulation does not prove each edge by direct binding.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"silica","display_name":"Silica and soluble silicon","entity_type_key":"chemical_species"}},{"dimension":"plain_language","value_text":"The response extended to downstream bone-development regulators.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Biological Silicon Stimulates Collagen Type 1 and Osteocalcin Synthesis in Human Osteoblast-Like Cells Through the BMP-2/Smad/RUNX2 Signaling Pathway. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27025722/ · DOI 10.1007/s12011-016-0686-3","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8383cb61-5fd9-5ed6-b89d-c09d87fd75d9","evidence_kind":"source_excerpt","locator":"Lines 152-158","start_line":152,"end_line":158,"excerpt":"## silica-smad-runx2\nThe response extended to downstream bone-development regulators.\nOrthosilicic acid increased phosphorylated SMAD1/5 and RUNX2 expression alongside osteogenic markers.\nModel: Human osteoblast-like cell lines, 10 micromolar exposure.\nLimitations: Marker regulation does not prove each edge by direct binding.\nEvidence access: Primary abstract\nBiological Silicon Stimulates Collagen Type 1 and Osteocalcin Synthesis in Human Osteoblast-Like Cells Through the BMP-2/Smad/RUNX2 Signaling Pathway. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27025722/ · DOI 10.1007/s12011-016-0686-3","model_system":"Human osteoblast-like cell lines, 10 micromolar exposure.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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