{"id":"ca50e54f-4f56-5752-9815-605ae2ec2420","stable_key":"dff9f743-3766-5f20-a71e-d6d2bd5bfb6f:va-retinoic-acid-precursor-rank","predicate":"suppresses","statement":"Retinoic acid suppressed RANK and RANKL-driven osteoclast differentiation in progenitor cultures.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"08e69019-159c-5e4f-b8fa-af4dfc2d9d8b","mechanism_event_label":"The response differs when the experiment starts with isolated precursor cells.","subject":{"id":"05487b29-8c59-5af8-83cf-cf9c79c5ecb8","slug":"all-trans-retinoic-acid","display_name":"All-trans-retinoic acid","entity_type_key":"small_molecule"},"object":{"id":"40043387-06a5-5ee5-8c8c-1d7b268490de","slug":"tnfrsf11a","display_name":"Receptor activator of NF-kappa-B / TNFRSF11A / RANK","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"08e69019-159c-5e4f-b8fa-af4dfc2d9d8b","stable_key":"dff9f743-3766-5f20-a71e-d6d2bd5bfb6f:va-retinoic-acid-precursor-rank-event","event_type":"biochemical_relationship","label":"The response differs when the experiment starts with isolated precursor cells.","description":"Retinoic acid suppressed RANK and RANKL-driven osteoclast differentiation in progenitor cultures.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"de7ad036-388f-596d-8766-72afe51b4a67","slug":"tnfsf11","display_name":"RANK ligand / TNFSF11","entity_type_key":"protein"},"role":"stimulus","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"11f2efac-c304-5731-8ebb-11864985e282","slug":"nfatc1","display_name":"NFATC1","entity_type_key":"protein"},"role":"downstream_transcription_factor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a4c1aaa0-3366-5bb2-bc5c-910241d8b64b","slug":"osteoclast-differentiation","display_name":"Osteoclast differentiation","entity_type_key":"cellular_process"},"role":"reduced_process","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"05487b29-8c59-5af8-83cf-cf9c79c5ecb8","slug":"all-trans-retinoic-acid","display_name":"All-trans-retinoic acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"40043387-06a5-5ee5-8c8c-1d7b268490de","slug":"tnfrsf11a","display_name":"Receptor activator of NF-kappa-B / TNFRSF11A / RANK","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Retinoid/bone-cell stage-dependent response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human and mouse osteoclast progenitors.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not negate whole-bone resorption results; cell stage and neighboring cells differ.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin A research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-a","display_name":"Vitamin A","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens; Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The response differs when the experiment starts with isolated precursor cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[va-hu2010] Retinoic acid increases proliferation of human osteoclast progenitors and inhibits RANKL-stimulated osteoclast differentiation by suppressing RANK (2010). https://pubmed.ncbi.nlm.nih.gov/20949013/ DOI: 10.1371/journal.pone.0013305","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Osteoclast precursors","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"61329ece-9362-5484-ba62-209c43ec74b3","evidence_kind":"source_excerpt","locator":"Lines 1638-1648","start_line":1638,"end_line":1648,"excerpt":"### va-retinoic-acid-precursor-rank\nRetinoic acid suppressed RANK and RANKL-driven osteoclast differentiation in progenitor cultures.\nCondition category: normal\nnutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The response differs when the experiment starts with isolated precursor cells.\norganism: Homo sapiens; Mus musculus\ntissue_or_cell_type: Osteoclast precursors\nexperimental_model: Human and mouse osteoclast progenitors.\nlimitations: Does not negate whole-bone resorption results; cell stage and neighboring cells differ.\ncross_nutrient: Retinoid/bone-cell stage-dependent response.\n[va-hu2010] Retinoic acid increases proliferation of human osteoclast progenitors and inhibits RANKL-stimulated osteoclast differentiation by suppressing RANK (2010). https://pubmed.ncbi.nlm.nih.gov/20949013/ DOI: 10.1371/journal.pone.0013305","model_system":"Human and mouse osteoclast progenitors.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [va-hu2010] Retinoic acid increases proliferation of human osteoclast progenitors and inhibits RANKL-stimulated osteoclast differentiation by suppressing RANK (2010). https://pubmed.ncbi.nlm.nih.gov/20949013/ DOI: 10.1371/journal.pone.0013305","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"0c5474e2-be48-547b-b287-9c07a59c9ff1","stable_key":"import-dff9f743-3766-5f20-a71e-d6d2bd5bfb6f","title":"Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"b217224b262abbd77d6a0c8c9beefff9c022fae4d31e2a5273915d769b9a6546","revision_id":"61008909-871f-575c-b5e2-21542689ea3c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}