ArticleInternational journal of surgery (London, England)2026
Systemic cachexia and muscle-bone crosstalk drive depression-related joint remodeling and pain.
Article in International journal of surgery (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundJoint pain is common in patients with depression, but its structural basis and molecular mechanisms remain unclear. This study aimed to investigate the underlying pathological changes and signaling pathways contributing to depression-related joint pain. MATERIALS AND
methodsUsing inflammatory and chronic stress-induced mouse models of depression, we evaluated osteoclast activation, subchondral bone remodeling, and associated behavioral alterations. Molecular and genetic analyses were conducted to examine the role of the Lbp-Tlr4-Netrin-1 signaling axis and key metabolic genes including Gdf-15, LepR, and PPARγ, specifically in adipose tissue, bone marrow, and osteoclasts. Additionally, we assessed the impact of muscle degeneration on joint pathology, and conditionally deleted TGF-β1 in muscle satellite cells to determine its role in joint preservation.
resultsDepression-induced joint pain was associated with increased osteoclast activity and extensive subchondral bone remodeling. The Lbp-Tlr4-Netrin-1 axis was highly upregulated in depressed subchondral bone, and its inhibition alleviated both pain-like behaviors and excessive bone resorption while mitigating depression-related weight loss. Deletion of Gdf-15, LepR, and PPARγ revealed that lipid metabolism genes significantly affect both depressive behavior and pain. Depression promoted TGF-β-mediated mesenchymal stem cell senescence and adipogenic differentiation, resembling pathological changes seen in aging and obesity. Notably, simple weight gain without metabolic correction worsened joint damage. Muscle wasting due to depression also contributed to joint pathology, and deletion of TGF-β1 in satellite cells improved joint integrity.
conclusionsDepression-related joint pain is not merely a psychological phenomenon but a complex organic disorder with defined structural and molecular underpinnings. It involves dysregulated lipid metabolism, aging-associated pathways, and multi-organ interactions between fat, muscle, bone, and the nervous system.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.