Component

RANK ligand / TNFSF11

Independent biological entity. Read linked claims for experimental scope and context.

9 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Soluble RANKL/ODF supported osteoclast-like-cell formation from mouse spleen precursors in the presence of M-CSF without osteoblast/stromal coculture.

    RANK ligand / TNFSF11 → Osteoclast differentiation source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Recombinant ligand culture assay
    limitations
    M-CSF and culture context are required; this is not a calcium-supplement response.
    nutrient_topic
    Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
    organism
    Mus musculus
    plain_language
    A bone-cell signal can instruct precursors to become bone-resorbing cells.
    primary_references
    [yasuda1998] Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC19881/ DOI: 10.1073/pnas.95.7.3597
    tissue_or_cell_type
    Spleen-derived osteoclast precursors

    Calcium: mechanism-first literature curation (2026-09-17) · lines 1036–1045

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant ligand culture assay · source_derived_draft · unverified_draft

    ### rankl-promotes-osteoclast-differentiation Soluble RANKL/ODF supported osteoclast-like-cell formation from mouse spleen precursors in the presence of M-CSF without osteoblast/stromal coculture. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A bone-cell signal can instruct precursors to become bone-resorbing cells. organism: Mus musculus tissue_or_cell_type: Spleen-derived osteoclast precursors experimental_model: Recombinant ligand culture assay limitations: M-CSF and culture context are required; this is not a calcium-supplement response. [yasuda1998] Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC19881/ DOI: 10.1073/pnas.95.7.3597
    Complete structured claim and evidence

What acts on it

  1. Calcitriol activated mouse Rankl transcription through distal VDR/RXR-associated regulatory regions, including a functional element about 76 kb upstream.

    Calcitriol → RANK ligand / TNFSF11 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Vitamin D–calcium–phosphate regulation.
    evidence_locator
    Abstract: reported experimental results
    evidence_scope
    D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
    experimental_model
    Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays
    exposure
    Calcitriol-treated cell and reporter systems; dose and time vary by experiment and are not specified in the retrieved abstract.
    limitations
    Enhancer activation is distinct from a fracture outcome. The human and mouse regulatory landscapes are not asserted to be identical.
    nutrient
    Vitamin D2 and D3 · Vitamin D2 and D3
    nutrient_topic
    Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
    organism
    Mus musculus
    plain_language
    Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions.
    primary_references
    [vdm-meyer2006rankl] Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. (2006). https://pubmed.ncbi.nlm.nih.gov/16914732/ DOI: 10.1128/mcb.00353-06
    tissue_or_cell_type
    Osteoblastic cell chromatin

    Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 841–855

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays · source_derived_draft · unverified_draft

    ### vdm-calcitriol-rankl-distal-enhancer Calcitriol activated mouse Rankl transcription through distal VDR/RXR-associated regulatory regions, including a functional element about 76 kb upstream. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions. organism: Mus musculus tissue_or_cell_type: Osteoblastic cell chromatin experimental_model: Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays limitations: Enhancer activation is distinct from a fracture outcome. The human and mouse regulatory landscapes are not asserted to be identical. exposure: Calcitriol-treated cell and reporter systems; dose and time vary by experiment and are not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-meyer2006rankl] Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. (2006). https://pubmed.ncbi.nlm.nih.gov/16914732/ DOI: 10.1128/mcb.00353-06
    Complete structured claim and evidence

  2. Osteoprotegerin bound RANKL/ODF and blocked its osteoclastogenic activity in the mouse culture system.

    Osteoprotegerin / TNFRSF11B / OPG → RANK ligand / TNFSF11 source_derived_draftungraded
    Experimental context and source evidence
    compartment_description
    Extracellular space
    experimental_model
    Ligand identification and inhibition assays
    limitations
    The experiment establishes ligand sequestration in this system, not clinical fracture protection.
    nutrient_topic
    Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
    organism
    Mus musculus cell system
    plain_language
    OPG can intercept the signal that promotes bone-resorbing cells.
    primary_references
    [yasuda1998] Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC19881/ DOI: 10.1073/pnas.95.7.3597
    tissue_or_cell_type
    Stromal and osteoclast-precursor cultures

    Calcium: mechanism-first literature curation (2026-09-17) · lines 1047–1057

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand identification and inhibition assays · source_derived_draft · unverified_draft

    ### opg-binds-rankl Osteoprotegerin bound RANKL/ODF and blocked its osteoclastogenic activity in the mouse culture system. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: OPG can intercept the signal that promotes bone-resorbing cells. organism: Mus musculus cell system tissue_or_cell_type: Stromal and osteoclast-precursor cultures experimental_model: Ligand identification and inhibition assays limitations: The experiment establishes ligand sequestration in this system, not clinical fracture protection. compartment_description: Extracellular space [yasuda1998] Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC19881/ DOI: 10.1073/pnas.95.7.3597
    Complete structured claim and evidence

  3. Retinoic acid increased RANKL and the RANKL/OPG ratio in mouse calvarial cultures; receptor-selective results implicated RARalpha.

    All-trans-retinoic acid → RANK ligand / TNFSF11 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Retinoid signaling -> calcium-store remodeling.
    experimental_model
    Neonatal mouse bone organ culture.
    limitations
    Receptor pharmacology is not proof of a human dietary effect.
    nutrient_topic
    Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
    organism
    Mus musculus
    plain_language
    A vitamin A metabolite increased a signal that promotes bone resorption.
    primary_references
    [va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734
    tissue_or_cell_type
    Calvarial bone

    Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1614–1624

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Neonatal mouse bone organ culture. · source_derived_draft · unverified_draft

    ### va-rar-alpha-rankl-bone Retinoic acid increased RANKL and the RANKL/OPG ratio in mouse calvarial cultures; receptor-selective results implicated RARalpha. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin A metabolite increased a signal that promotes bone resorption. organism: Mus musculus tissue_or_cell_type: Calvarial bone experimental_model: Neonatal mouse bone organ culture. limitations: Receptor pharmacology is not proof of a human dietary effect. cross_nutrient: Retinoid signaling -> calcium-store remodeling. [va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. In long-term adult human primary osteoblast cultures, strontium ranelate increased the OPG/RANKL ratio and an OPG secretory response.

    Strontium ranelate → Osteoprotegerin / TNFRSF11B / OPG source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human culture, OPG ELISA and gene-expression assays.
    limitations
    Ratio change is not itself a direct measurement of osteoclast resorption.
    nutrient_topic
    Strontium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Strontium
    plain_language
    Bone-forming cells can change the signals reaching bone-resorbing cells.
    primary_references
    Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18763010/ · DOI 10.1007/s00198-008-0728-6

    Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 198–204

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human culture, OPG ELISA and gene-expression assays. · source_derived_draft · unverified_draft

    ## strontium-human-opg Bone-forming cells can change the signals reaching bone-resorbing cells. In long-term adult human primary osteoblast cultures, strontium ranelate increased the OPG/RANKL ratio and an OPG secretory response. Model: Human culture, OPG ELISA and gene-expression assays. Limitations: Ratio change is not itself a direct measurement of osteoclast resorption. Evidence access: Primary abstract Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18763010/ · DOI 10.1007/s00198-008-0728-6
    Complete structured claim and evidence

  2. A calcium-deficient diet increased osteoclasts and bone loss in adult mice; osteocyte-directed Rankl deletion blunted the response.

    Calcium → Osteoclastic bone resorption source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    experimental_model
    30 days of 0.01% versus 0.516% dietary calcium
    limitations
    Mouse diet and Cre-targeting scope limit human generalization; bone loss was blunted, not necessarily abolished.
    nutrient_topic
    Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
    organism
    Mus musculus
    plain_language
    When dietary calcium was severely restricted, osteocyte RANKL helped drive withdrawal from bone.
    primary_references
    [xiong2014] Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4125539/ DOI: 10.1016/j.bone.2014.06.006
    tissue_or_cell_type
    Adult cortical and cancellous bone
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Calcium: mechanism-first literature curation (2026-09-17) · lines 1070–1079

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 30 days of 0.01% versus 0.516% dietary calcium · source_derived_draft · unverified_draft

    ### low-calcium-diet-osteocyte-rankl-resorption A calcium-deficient diet increased osteoclasts and bone loss in adult mice; osteocyte-directed Rankl deletion blunted the response. Condition category: nutrient_deficiency nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: When dietary calcium was severely restricted, osteocyte RANKL helped drive withdrawal from bone. organism: Mus musculus tissue_or_cell_type: Adult cortical and cancellous bone experimental_model: 30 days of 0.01% versus 0.516% dietary calcium limitations: Mouse diet and Cre-targeting scope limit human generalization; bone loss was blunted, not necessarily abolished. [xiong2014] Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4125539/ DOI: 10.1016/j.bone.2014.06.006
    Complete structured claim and evidence

  3. Rank-null mice lacked osteoclasts and developed osteopetrosis; marrow transplantation or receptor re-expression restored osteoclast development.

    Receptor activator of NF-kappa-B / TNFRSF11A / RANK → Osteoclast differentiation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Rank-null mice and genetic rescue
    limitations
    Complete receptor loss is a machinery defect, not evidence of nutritional calcium deficiency.
    nutrient_topic
    Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
    organism
    Mus musculus
    plain_language
    RANK is necessary for normal formation of bone-resorbing cells in this mouse model.
    primary_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
    tissue_or_cell_type
    Bone and hematopoietic precursors
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Calcium: mechanism-first literature curation (2026-09-17) · lines 1059–1068

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rank-null mice and genetic rescue · source_derived_draft · unverified_draft

    ### rank-loss-blocks-osteoclast-formation Rank-null mice lacked osteoclasts and developed osteopetrosis; marrow transplantation or receptor re-expression restored osteoclast development. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: RANK is necessary for normal formation of bone-resorbing cells in this mouse model. organism: Mus musculus tissue_or_cell_type: Bone and hematopoietic precursors experimental_model: Rank-null mice and genetic rescue limitations: Complete receptor loss is a machinery defect, not evidence of nutritional calcium deficiency. [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
    Complete structured claim and evidence

  4. Exogenous OPG blocked retinoic-acid-stimulated labelled calcium release from calvarial bone.

    Osteoprotegerin / TNFRSF11B / OPG → Osteoclastic bone resorption source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Vitamin A/RANKL -> calcium release.
    experimental_model
    Same organ culture.
    limitations
    Preparation-specific causal intervention.
    nutrient_topic
    Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
    organism
    Mus musculus
    plain_language
    Blocking the RANKL signal interrupted the measured resorption response.
    primary_references
    [va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734
    tissue_or_cell_type
    Bone

    Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1626–1636

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same organ culture. · source_derived_draft · unverified_draft

    ### va-opg-blocks-retinoid-calcium-release Exogenous OPG blocked retinoic-acid-stimulated labelled calcium release from calvarial bone. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking the RANKL signal interrupted the measured resorption response. organism: Mus musculus tissue_or_cell_type: Bone experimental_model: Same organ culture. limitations: Preparation-specific causal intervention. cross_nutrient: Vitamin A/RANKL -> calcium release. [va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734
    Complete structured claim and evidence

  5. Retinoic acid suppressed RANK and RANKL-driven osteoclast differentiation in progenitor cultures.

    All-trans-retinoic acid → Receptor activator of NF-kappa-B / TNFRSF11A / RANK source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Retinoid/bone-cell stage-dependent response.
    experimental_model
    Human and mouse osteoclast progenitors.
    limitations
    Does not negate whole-bone resorption results; cell stage and neighboring cells differ.
    nutrient_topic
    Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
    organism
    Homo sapiens; Mus musculus
    plain_language
    The response differs when the experiment starts with isolated precursor cells.
    primary_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
    tissue_or_cell_type
    Osteoclast precursors

    Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1638–1648

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and mouse osteoclast progenitors. · source_derived_draft · unverified_draft

    ### va-retinoic-acid-precursor-rank Retinoic acid suppressed RANK and RANKL-driven osteoclast differentiation in progenitor cultures. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response differs when the experiment starts with isolated precursor cells. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Osteoclast precursors experimental_model: Human and mouse osteoclast progenitors. limitations: Does not negate whole-bone resorption results; cell stage and neighboring cells differ. cross_nutrient: Retinoid/bone-cell stage-dependent response. [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
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards