Diacerein reduces the excess synthesis of bone remodeling factors by human osteoblast cells from osteoarthritic subchondral bone.
Bibliographic record
Abstract
OBJECTIVE: Although cartilage degradation characterizes osteoarthritis (OA), there is evidence that remodeling of subchondral bone in this disease is a contributing factor. Therapeutic strategies to modify the metabolism of subchondral bone osteoblasts may be indicated to treat OA. We studied the effects of diacerein and rhein on the metabolic and inflammatory variables of OA subchondral osteoblasts. METHODS: Human OA primary subchondral osteoblast cells were used. The effect of diacerein and rhein at therapeutic concentrations (5-20 microg/ml) was determined by osteoblast phenotypic factors, alkaline phosphatase, osteocalcin, and cAMP; on metabolic agents urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and insulin-like growth factor-1 (IGF-1); and on inflammatory mediators interleukin 6 (IL-6), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2). RESULTS: Diacerein and rhein did not affect either basal and 1,25(OH)2D3 induced alkaline phosphatase or parathyroid hormone (PTH) stimulated cAMP formation. Conversely, they dose dependently and statistically inhibited 1,25(OH)2D3 induced osteocalcin release, a situation explained by a reduction of mRNA levels for osteocalcin. Of the metabolic factors, they inhibited the production of uPA, with rhein showing slightly more potency; inhibitions of 69% and 57% were reached at the highest concentration (20 microg/ml) of rhein and diacerein, respectively. Both drugs also inhibited the PAI-1 level, albeit at a much lower level than for uPA. Interestingly, determination of the uPA/PAI1 ratio revealed that both drugs inhibited it about 55%, suggesting a decrease in uPA activity. In contrast, IGF-1 levels only increased slightly when cells were treated with rhein but not with diacerein. A transient dose dependent effect was found on IL-6 production; an inhibition was noted at low drug concentrations, which returned to basal levels at the highest concentration tested. PGE2 levels increased exponentially and were related to a concomitant increase in COX-2 levels in response to both drugs. CONCLUSION: Our data indicate that diacerein and rhein do not appear to affect OA subchondral bone cells' basal cellular metabolism, yet both agents reveal a direct effect at reducing the synthetic activities of osteoblasts, which could be responsible for abnormal subchondral bone remodeling occurring during the course of 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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) | 0.002 | 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".