{"id":"34a02caf-c9fd-5978-aa8c-fd3030a76878","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:rank-loss-blocks-osteoclast-formation","predicate":"required_for","statement":"Rank-null mice lacked osteoclasts and developed osteopetrosis; marrow transplantation or receptor re-expression restored osteoclast development.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"ade95fdc-4ba2-5a32-a8db-c013c1b65806","mechanism_event_label":"RANK is necessary for normal formation of bone-resorbing cells in this mouse model.","subject":{"id":"40043387-06a5-5ee5-8c8c-1d7b268490de","slug":"tnfrsf11a","display_name":"Receptor activator of NF-kappa-B / TNFRSF11A / RANK","entity_type_key":"protein"},"object":{"id":"a4c1aaa0-3366-5bb2-bc5c-910241d8b64b","slug":"osteoclast-differentiation","display_name":"Osteoclast differentiation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ade95fdc-4ba2-5a32-a8db-c013c1b65806","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:rank-loss-blocks-osteoclast-formation-event","event_type":"biochemical_relationship","label":"RANK is necessary for normal formation of bone-resorbing cells in this mouse model.","description":"Rank-null mice lacked osteoclasts and developed osteopetrosis; marrow transplantation or receptor re-expression restored osteoclast development.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"40043387-06a5-5ee5-8c8c-1d7b268490de","slug":"tnfrsf11a","display_name":"Receptor activator of NF-kappa-B / TNFRSF11A / RANK","entity_type_key":"protein"},"role":"deleted_and_restored_receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"de7ad036-388f-596d-8766-72afe51b4a67","slug":"tnfsf11","display_name":"RANK ligand / TNFSF11","entity_type_key":"protein"},"role":"receptor_ligand_context","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":"affected_process","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"0adc6543-b0c1-5a49-9428-80f727ffeb9a","slug":"bone-resorption","display_name":"Osteoclastic bone resorption","entity_type_key":"cellular_process"},"role":"downstream_process","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":"experimental_model","value_text":"Rank-null mice and genetic rescue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Complete receptor loss is a machinery defect, not evidence of nutritional calcium deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Calcium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"calcium","display_name":"Calcium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"RANK is necessary for normal formation of bone-resorbing cells in this mouse model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[li2000] RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism (2000). https://pubmed.ncbi.nlm.nih.gov/10677500/ DOI: 10.1073/pnas.97.4.1566","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Bone and hematopoietic precursors","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":"6b569f88-103b-52ec-b516-393caa03a2f0","evidence_kind":"source_excerpt","locator":"Lines 1059-1068","start_line":1059,"end_line":1068,"excerpt":"### rank-loss-blocks-osteoclast-formation\nRank-null mice lacked osteoclasts and developed osteopetrosis; marrow transplantation or receptor re-expression restored osteoclast development.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: RANK is necessary for normal formation of bone-resorbing cells in this mouse model.\norganism: Mus musculus\ntissue_or_cell_type: Bone and hematopoietic precursors\nexperimental_model: Rank-null mice and genetic rescue\nlimitations: Complete receptor loss is a machinery defect, not evidence of nutritional calcium deficiency.\n[li2000] RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism (2000). https://pubmed.ncbi.nlm.nih.gov/10677500/ DOI: 10.1073/pnas.97.4.1566","model_system":"Rank-null mice and genetic rescue","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [li2000] RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism (2000). https://pubmed.ncbi.nlm.nih.gov/10677500/ DOI: 10.1073/pnas.97.4.1566","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3c083fa0-59c6-50e9-af42-678d0e3c1006","stable_key":"import-434e1e27-eb90-583a-956b-62472726ffba","title":"Calcium: mechanism-first literature curation (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":"965c934d6b147f2b62f8d45ce6d7a87681a600bfe5c46a585b4704889afd3fc1","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}