Advanced glycation endproducts in the development of osteoarthritis
Bibliographic record
Abstract
Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting the elderly. The most prominent feature of OA is the progressive destruction of articular cartilage resulting in impaired joint motion, severe pain and, ultimately, disability. Age is identified as the main risk factor for the development of OA, but the mechanism by which aging is involved still remains largely unclear. Age-related changes in the articular cartilage could play an important role in the susceptibility of cartilage to OA. One of the major age-related changes in articular cartilage is the accumulation of advanced glycation endproducts (AGEs), resulting from the spontaneous reaction of reducing sugars with proteins. The present studies were designed to investigate whether AGE accumulation in cartilage may predispose to the development of OA. The role of AGEs in the development of OA was studied by a combination of in vitro , ex vivo and in vivo experiments. The type and quantity of AGEs in human articular cartilage were determined using HPLC and GC-MS methods. Effects of AGE accumulation on cartilage extracellular matrix turnover were assessed in human articular cartilage and bovine alginate cultures using radiolabel incorporation, colorimetric, enzyme activity and HPLC analyses. The in vivo role of AGEs in OA predisposition was studied in the canine ACLT model for OA. High levels of all well-characterized AGEs (pentosidine, carboxymethyllysine and carboxyethyllysine) accumulate with age in cartilage collagen. Furthermore, an age-related increase of general measures of AGEs (fluorescence at 370/440 nm, browning, and amino acid modification) was also observed [ 1 ]. Accumulation of AGEs was correlated with increased stiffness and brittleness of the cartilage, rendering it more prone to mechanical damage. In addition to affecting the mechanical properties of tissues, articular cartilage chondrocytes show decreased proteoglycan and collagen synthesis at increased AGE levels. Degradation of AGE-modified collagen by matrix metalloproteinases is impaired compared with unmodified collagen. In a canine study of experimentally induced OA by anterior cruciate ligament transection, animals with elevated AGE levels suffered from more severe OA than those with normal AGE levels [ 2 ]. Moreover, in a cross-sectional study using human articular cartilage samples obtained at autopsy, the presence of cartilage degeneration was associated with higher AGE levels in the joint cartilage. AGE accumulation in cartilage leads to decreased mechanical properties (increased stiffness and brittleness) and impaired extracellular matrix turnover (decreased synthesis and degradation). Together these data support the hypothesis presented in Fig. 1 that the age-related accumulation of AGEs changes the properties of articular cartilage and thereby renders the tissue more prone to the development of OA. Hypothesis of how advanced glycation endproduct (AGE)-related accumulation of AGEs could predispose to the development of osteoarthritis (OA).
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".