Elevated expression of periostin in human osteoarthritic cartilage and its potential role in matrix degradation <i>via</i> matrix metalloproteinase‐13
Bibliographic record
Abstract
ABSTRACT We investigated the role of periostin, an extracellular matrix protein, in the pathophysiology of osteoarthritis (OA). In OA, dysregulated gene expression and phenotypic changes in articular chondrocytes culminate in progressive loss of cartilage from the joint surface. The molecular mechanisms underlying this process are poorly understood. We examined periostin expression by immunohistochemical analysis of lesional and nonlesional cartilage from human and rodent OA knee cartilage. In addition, we used small interfering (si) RNA and adenovirus transduction of chondrocytes to knock down and up‐regulate periostin levels, respectively, and analyzed its effect on matrix metalloproteinase (MMP)‐13, a disintegrin and MMP with thrombospondin motifs (ADAMTS)‐4, and type II collagen expression. We found high periostin levels in human and rodent OA cartilage. Periostin increased MMP‐13 expression dose [1‐10 μg/ml (EC 50 0.5‐1 μg/ml)] and time (24‐72 h) dependently, significantly enhanced expression of ADAMTS4 mRNA, and promoted cartilage degeneration through collagen and proteoglycan degradation. Periostin induction of MMP‐13 expression was inhibited by CCT031374 hydrobromide, an inhibitor of the canonical Wnt/β‐catenin signaling pathway. In addition, siRNA‐mediated knockdown of endogenous periostin blocked constitutive MMP‐13 expression. These findings implicate periostin as a catabolic protein that promotes cartilage degeneration in OA by up‐regulating MMP‐13 through canonical Wnt signaling.—Attur, M., Yang, Q., Shimada, K., Tachida, Y., Nagase, H., Mignatti, P., Statman, L., Palmer, G., Kirsch, T., Beier, F., Abramson, A. B. Elevated expression of periostin in human osteoarthritic cartilage and its potential role in matrix degradation via matrix metalloproteinase‐13. FASEB J. 29, 4107‐4121 (2015). www.fasebj.org
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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 | 0.001 | 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) | 0.000 | 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 teacher head, 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".