GDF15 mediates inflammation-associated bone loss through a brain-bone axis
Bibliographic record
Abstract
Abstract Metabolic mediators play an important role in regulating inflammation(1). Rheumatoid arthritis and spondyloarthritis are common inflammatory diseases of the joint, aggravated in context of obesity(2). These patients experience systemic bone loss(3,4), which is not sufficiently controlled by disease-modifying therapeutics, despite adequate control of inflammation(5,6). Here we report an unexpected role for GDF15 (Growth Differentiation Factor 15), a central mediator of food intake(7–10), in inflammation-associated bone loss. Serum GDF15 levels were found to be elevated in arthritis patients and inversely correlated with bone density. However, GDF15 itself does not appear to promote arthritis. Rather, GDF15 mediates trabecular bone loss through its receptor GFRAL, which is expressed exclusively in the hindbrain(7–10). GDF15-GFRAL binding results in β-adrenergic activation of bone Marrow Adipogenic Lineage Precursors (MALPs), mesenchymal cells which are known to stimulate osteoclasts and trigger bone loss(11–14). These data demonstrate how a metabolic mediator controls bone loss through a brain-bone axis in inflammatory diseases. These findings may lead to more specific therapeutic interventions to protect bone through targeting GDF15 or MALPs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.002 |
| Research integrity | 0.002 | 0.006 |
| Insufficient payload (model declined to judge) | 0.001 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".