Sexual dimorphism in reactive oxygen species production and a role for integrin α1β1 in estrogen receptor α and β expression in articular cartilage
Bibliographic record
Abstract
BACKGROUND: Osteoarthritis (OA) is a debilitating disease involving cartilage degradation. A need remains for the discovery of new molecular targets in cartilage for pharmaceutical intervention of OA. One potential target is integrin α1β1 that protects against OA when it is upregulated by chondrocytes early in the disease process. Integrin α1β1 offers this protection by dampening epidermal growth factor receptor (EGFR) signaling, and its effects are more robust in females compared to males. The aim of this study, therefore, was to measure the impact of itga1 on chondrocyte EGFR activity and downstream reactive oxygen species (ROS) production in male and female mice. Furthermore, chondrocyte expression of estrogen receptor (ER) α and ERβ was measured to investigate the mechanism for sexual dimorphism in the EGFR/integrin α1β1 signaling axis. We hypothesized that integrin α1β1 would decrease ROS production and pEGFR and 3-nitrotyrosine expression, with this effect being greater in females. We further hypothesized that chondrocyte expression of ERα and ERβ would be greater in females compared to males, with a greater effect seen in itga1-null compared to wild-type mice. MATERIALS AND METHODS: Femoral and tibial cartilage of male and female, wild-type and itga1-null mice were processed for ex vivo confocal imaging of ROS, immunohistochemical analysis of 3-nitrotyrosine, or immunofluorescence of pEGFR and ERα and ERβ. RESULTS: We show that ROS-producing chondrocytes are more abundant in female itga1-null compared to wild-type mice ex vivo; however, itga1 had limited influence on the percent of chondrocytes stained positively for 3-nitrotyrosine or pEGFR in situ. In addition, we found that itga1 influenced ERα and ERβ expression in femoral cartilage from female mice, and that ERα and ERβ were coexpressed as well as colocalized in chondrocytes. Finally, we show sexual dimorphism in ROS and 3-nitrotyrosine production, but surprisingly not in pEGFR expression. CONCLUSIONS: Together these data highlight sexual dimorphism in the EGFR/integrin α1β1 signaling axis and underline the need for further investigation into the role of ERs in this biological paradigm. Understanding the molecular mechanisms underlying the development of OA is essential for the development of individualized, sex-specific treatments in this age of personalized medicine.
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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".