Dysregulation of ERK signaling in CD4-expressing cells induces osteochondromas
Bibliographic record
Abstract
Abstract ERK1 and ERK2 are serine/threonine kinases critical for the proliferation and development of many cell types. Mice with a germline deletion of Erk1 bred to mice with a conditional deletion of Erk2 mediated by CD4cre (DKOCD4 mice) exhibit a profound block in T cell development in the thymus. Surprisingly, 80% of DKOCD4 mice spontaneously developed osteochondromas by 28 weeks of age. Histological analysis of these lesions revealed excessive accumulation of hypertrophic chondrocytes originating from the growth plates in the bone, but no mononuclear infiltrate indicative of inflammation. As the majority of CD4+ cells are T cells, we investigated whether these lesions were caused by deletion of Erk2 in T cells by breeding the DKOCD4 mice to Rag1 − / − mice. Unexpectedly, osteochondromas still appeared in DKOCD4 Rag1 − / − mice. In fact, osteochondromas developed faster and were more severe in DKOCD4 Rag1 − / − mice compared to DKOCD4 mice, indicating that deletion of Erk2 in other cell types mediates excess cartilage accumulation. Furthermore, the addition of T cells to DKOCD4 Rag1 − / − mice delayed development of osteochondromas, showing that T cells play an important role in regulating cartilage homeotstasis. Furthermore, the development of the osteochondromas appears to be influenced by changes in the microbiota, as DKOCD4 mice treated with an antibiotic cocktail have a delay in osteochondroma development, while mice housed in non-specific pathogen free conditions had accelerated onset of tumors. Together these data suggest that Erk plays a critical role in a CD4+ cell type other than T cells, possibly an innate lymphoid cell, to alter cartilage growth. In addition, we present a novel role for T cells in regulating cartilage homeostasis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".