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Diacerein protects against iodoacetate-induced osteoarthritis in the femorotibial joints of rats.

Jain A, Singh R, Singh S, Singh S - J Biomed Res (2015)

Bottom Line: Based on histopathological and biochemical findings, diacerein treatment showed chondroprotective effect.Furthermore, the chondroprotective effect of diacerein was found to be more pronounced after 12 weeks as compared to 8 weeks in both cases (i.e., post 1 and 2 weeks of iodoacetate injection).Similar results were observed by investigation of chondroitin sulfate during biochemical study, showing the chondroprotective effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Indian Institute of Technology ; National Institute of Pharmaceutical Education & Research , Raebareli-229 010, U.P. India.

ABSTRACT
The present study was undertaken to investigate the effect of diacerein on the histopathology of articular cartilage and subchondral bone of the femorotibial joint in rats. Osteoarthritis was induced in rats after single intra-articular injection of sodium iodoacetate. Rats were sacrificed 1, 2, 4, and 8 weeks post intra-articular injection to evaluate the progression of histopathogenesis of osteoarthritis. Diacerein was orally administered (15 mg/kg) once daily post 1 and 2 weeks of iodoacetate injection in two groups, respectively, for up to 12 weeks. Articular cartilage and subchondral bone of the rats of both groups were examined after 8 and 12 weeks, respectively. Quantitative histological analyses were performed by scoring these sections as per the OARSI system. Chondroitin sulfate was also estimated in articular cartilage by decrease in absorbance of methylene blue on complexation with chondroitin sulfate using a spectrophotometer. Intra-articular injection of iodoacetate induced loss of articular cartilage with progressive subchondral bone sclerosis and degeneration. Based on histopathological and biochemical findings, diacerein treatment showed chondroprotective effect. Furthermore, the chondroprotective effect of diacerein was found to be more pronounced after 12 weeks as compared to 8 weeks in both cases (i.e., post 1 and 2 weeks of iodoacetate injection). Similar results were observed by investigation of chondroitin sulfate during biochemical study, showing the chondroprotective effect. In conclusion, diacerein exhibits chondroprotective effect in rats with late onset of action.

No MeSH data available.


Related in: MedlinePlus

Progression of disease (OA) after IA injection.A and B: Femorotibial joint 2 weeks post IA injection. The articular surface exhibits multifocal denuded cartilage with fissures extending deep into the mid zone. Large numbers of necrotic chondrocytes are seen (White arrow head). C: Chondrocytes degeneration exhibited by empty chondrons in the surface cartilage (White arrow); (Grade 3-3.5, Stage 3). H&E, A x100, B,C x400. D and E: Femoral condyle 4 weeks post IA injection showing marked loss of cartilage from the surface associated with subchondral bone collapse and fragmentation. Large areas of subchondral hemopoietic tissue are replaced by fibrous tissue (*). Marked bony trabeculae loss and collapse leading to formation of large interosseous spaces (black triangle) are seen. F: Irregular margin of the surface cartilage is visualized as well as irregular margin of the matrix of the regenerative fibrocartilage. (White asterisk), (Grade 4-4.5, Stage 3). H & E. D x100.E,F x400. 2G-Tibial condyle 8 weeks post IA injection showing extensive degeneration of the articular cartilage and the subchondral bone (arrow head) H and I: Complete loss of the cartilage and large cysts within the subchondral region (*). Articular cartilage erosion (arrow). Cortical area show fibrous tissue formation (double arrow). Associated large number of degenerative (necrotic) chondrocytes (arrow head). Regeneration of chondrocytes cell nest dispersed without normal arrangement (triangle). Subchondral cyst due to cartilage cell proiferation within the subchodral bone (*), (Garde 5-5.5, Stage 4). H & E.x20, x100, x400.
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f02: Progression of disease (OA) after IA injection.A and B: Femorotibial joint 2 weeks post IA injection. The articular surface exhibits multifocal denuded cartilage with fissures extending deep into the mid zone. Large numbers of necrotic chondrocytes are seen (White arrow head). C: Chondrocytes degeneration exhibited by empty chondrons in the surface cartilage (White arrow); (Grade 3-3.5, Stage 3). H&E, A x100, B,C x400. D and E: Femoral condyle 4 weeks post IA injection showing marked loss of cartilage from the surface associated with subchondral bone collapse and fragmentation. Large areas of subchondral hemopoietic tissue are replaced by fibrous tissue (*). Marked bony trabeculae loss and collapse leading to formation of large interosseous spaces (black triangle) are seen. F: Irregular margin of the surface cartilage is visualized as well as irregular margin of the matrix of the regenerative fibrocartilage. (White asterisk), (Grade 4-4.5, Stage 3). H & E. D x100.E,F x400. 2G-Tibial condyle 8 weeks post IA injection showing extensive degeneration of the articular cartilage and the subchondral bone (arrow head) H and I: Complete loss of the cartilage and large cysts within the subchondral region (*). Articular cartilage erosion (arrow). Cortical area show fibrous tissue formation (double arrow). Associated large number of degenerative (necrotic) chondrocytes (arrow head). Regeneration of chondrocytes cell nest dispersed without normal arrangement (triangle). Subchondral cyst due to cartilage cell proiferation within the subchodral bone (*), (Garde 5-5.5, Stage 4). H & E.x20, x100, x400.

Mentions: The progression of disease is shown in Fig. 2. Different stages of moderate to advanced OA were seen due to the metabolic inhibitory effect of iodoacetate. Two weeks post iodoacetate treatment, the tissues completely broke down (Fig. 2A, B, and C). Multifocal, denuded cartilage was observed with a large number of necrotic chondrocytes. Deep fissures and cracks were observed, which reached down to the deep calcified zone. Moreover, chondrocyte degeneration was found on the surface layer, which was clearly evidenced by the empty chondrons. Four weeks post iodoacetate treatment, advanced stages of OA were observed (Fig. 2D, E, and F), marked by loss of surface cartilage with subchondral bone collapse and fragmentation. Subchondral hemopoetic tissues were replaced by fibrous tissue. The bony trabeculae collapsed due to extreme thinning and degeneration, which led to an increase in interosseous space, (Fig. 2D, E). Eight weeks post iodoacetate treatment (Fig. 2G, H, and I), there was well-defined subchondral cyst formation within the subchondral bone, demarcated by fibrous tissue. Regenerated chondrocyte cell nests were dispersed without normal arrangements. A large number of degenerative necrotic chondrocytes with pyknotic nuclei and sometimes partly dissolved cytoplasm were present. An increase in interosseous spaces, with a break in the bony spicules in between, resulted in confluence of the interosseous space and large cyst formation.


Diacerein protects against iodoacetate-induced osteoarthritis in the femorotibial joints of rats.

Jain A, Singh R, Singh S, Singh S - J Biomed Res (2015)

Progression of disease (OA) after IA injection.A and B: Femorotibial joint 2 weeks post IA injection. The articular surface exhibits multifocal denuded cartilage with fissures extending deep into the mid zone. Large numbers of necrotic chondrocytes are seen (White arrow head). C: Chondrocytes degeneration exhibited by empty chondrons in the surface cartilage (White arrow); (Grade 3-3.5, Stage 3). H&E, A x100, B,C x400. D and E: Femoral condyle 4 weeks post IA injection showing marked loss of cartilage from the surface associated with subchondral bone collapse and fragmentation. Large areas of subchondral hemopoietic tissue are replaced by fibrous tissue (*). Marked bony trabeculae loss and collapse leading to formation of large interosseous spaces (black triangle) are seen. F: Irregular margin of the surface cartilage is visualized as well as irregular margin of the matrix of the regenerative fibrocartilage. (White asterisk), (Grade 4-4.5, Stage 3). H & E. D x100.E,F x400. 2G-Tibial condyle 8 weeks post IA injection showing extensive degeneration of the articular cartilage and the subchondral bone (arrow head) H and I: Complete loss of the cartilage and large cysts within the subchondral region (*). Articular cartilage erosion (arrow). Cortical area show fibrous tissue formation (double arrow). Associated large number of degenerative (necrotic) chondrocytes (arrow head). Regeneration of chondrocytes cell nest dispersed without normal arrangement (triangle). Subchondral cyst due to cartilage cell proiferation within the subchodral bone (*), (Garde 5-5.5, Stage 4). H & E.x20, x100, x400.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4585436&req=5

f02: Progression of disease (OA) after IA injection.A and B: Femorotibial joint 2 weeks post IA injection. The articular surface exhibits multifocal denuded cartilage with fissures extending deep into the mid zone. Large numbers of necrotic chondrocytes are seen (White arrow head). C: Chondrocytes degeneration exhibited by empty chondrons in the surface cartilage (White arrow); (Grade 3-3.5, Stage 3). H&E, A x100, B,C x400. D and E: Femoral condyle 4 weeks post IA injection showing marked loss of cartilage from the surface associated with subchondral bone collapse and fragmentation. Large areas of subchondral hemopoietic tissue are replaced by fibrous tissue (*). Marked bony trabeculae loss and collapse leading to formation of large interosseous spaces (black triangle) are seen. F: Irregular margin of the surface cartilage is visualized as well as irregular margin of the matrix of the regenerative fibrocartilage. (White asterisk), (Grade 4-4.5, Stage 3). H & E. D x100.E,F x400. 2G-Tibial condyle 8 weeks post IA injection showing extensive degeneration of the articular cartilage and the subchondral bone (arrow head) H and I: Complete loss of the cartilage and large cysts within the subchondral region (*). Articular cartilage erosion (arrow). Cortical area show fibrous tissue formation (double arrow). Associated large number of degenerative (necrotic) chondrocytes (arrow head). Regeneration of chondrocytes cell nest dispersed without normal arrangement (triangle). Subchondral cyst due to cartilage cell proiferation within the subchodral bone (*), (Garde 5-5.5, Stage 4). H & E.x20, x100, x400.
Mentions: The progression of disease is shown in Fig. 2. Different stages of moderate to advanced OA were seen due to the metabolic inhibitory effect of iodoacetate. Two weeks post iodoacetate treatment, the tissues completely broke down (Fig. 2A, B, and C). Multifocal, denuded cartilage was observed with a large number of necrotic chondrocytes. Deep fissures and cracks were observed, which reached down to the deep calcified zone. Moreover, chondrocyte degeneration was found on the surface layer, which was clearly evidenced by the empty chondrons. Four weeks post iodoacetate treatment, advanced stages of OA were observed (Fig. 2D, E, and F), marked by loss of surface cartilage with subchondral bone collapse and fragmentation. Subchondral hemopoetic tissues were replaced by fibrous tissue. The bony trabeculae collapsed due to extreme thinning and degeneration, which led to an increase in interosseous space, (Fig. 2D, E). Eight weeks post iodoacetate treatment (Fig. 2G, H, and I), there was well-defined subchondral cyst formation within the subchondral bone, demarcated by fibrous tissue. Regenerated chondrocyte cell nests were dispersed without normal arrangements. A large number of degenerative necrotic chondrocytes with pyknotic nuclei and sometimes partly dissolved cytoplasm were present. An increase in interosseous spaces, with a break in the bony spicules in between, resulted in confluence of the interosseous space and large cyst formation.

Bottom Line: Based on histopathological and biochemical findings, diacerein treatment showed chondroprotective effect.Furthermore, the chondroprotective effect of diacerein was found to be more pronounced after 12 weeks as compared to 8 weeks in both cases (i.e., post 1 and 2 weeks of iodoacetate injection).Similar results were observed by investigation of chondroitin sulfate during biochemical study, showing the chondroprotective effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Indian Institute of Technology ; National Institute of Pharmaceutical Education & Research , Raebareli-229 010, U.P. India.

ABSTRACT
The present study was undertaken to investigate the effect of diacerein on the histopathology of articular cartilage and subchondral bone of the femorotibial joint in rats. Osteoarthritis was induced in rats after single intra-articular injection of sodium iodoacetate. Rats were sacrificed 1, 2, 4, and 8 weeks post intra-articular injection to evaluate the progression of histopathogenesis of osteoarthritis. Diacerein was orally administered (15 mg/kg) once daily post 1 and 2 weeks of iodoacetate injection in two groups, respectively, for up to 12 weeks. Articular cartilage and subchondral bone of the rats of both groups were examined after 8 and 12 weeks, respectively. Quantitative histological analyses were performed by scoring these sections as per the OARSI system. Chondroitin sulfate was also estimated in articular cartilage by decrease in absorbance of methylene blue on complexation with chondroitin sulfate using a spectrophotometer. Intra-articular injection of iodoacetate induced loss of articular cartilage with progressive subchondral bone sclerosis and degeneration. Based on histopathological and biochemical findings, diacerein treatment showed chondroprotective effect. Furthermore, the chondroprotective effect of diacerein was found to be more pronounced after 12 weeks as compared to 8 weeks in both cases (i.e., post 1 and 2 weeks of iodoacetate injection). Similar results were observed by investigation of chondroitin sulfate during biochemical study, showing the chondroprotective effect. In conclusion, diacerein exhibits chondroprotective effect in rats with late onset of action.

No MeSH data available.


Related in: MedlinePlus