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Meloxicam ameliorates the cartilage and subchondral bone deterioration in monoiodoacetate-induced rat osteoarthritis

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ABSTRACT

Objective: This study aimed to quantify the cartilage- and subchondral bone-related effects of low-dose and high-dose meloxicam treatment in the late phase of mono-iodoacetate-induced osteoarthritis of the stifle.

Methods: Thirty-four male Wistar rats received intra-articular injection of mono-iodoacetate to trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono-iodoacetate-injected rats were assigned to three groups and treated from week 4 to the end of week 7 with placebo (Grp P, n = 11), low-dose (GrpM Lo, 0.2 mg/kg, n = 12) or high-dose (GrpM Hi, 1 mg/kg, n = 11) meloxicam. After a period of 4 additional weeks (end of week 11) the animals were sacrificed, and the stifle joints were examined histologically and immunohistochemically for cyclooxygenase 2, in conformity with recommendations of the Osteoarthritis Research Society International. Serum cytokines IL-6, TNFα and IL-10 were measured at the end of weeks 3, 7, and 11.

Results: Compared with saline-treated controls, animals treated with mono-iodoacetate developed various degrees of osteoarthritis. The cartilage degeneration score and the total cartilage degeneration width were significantly lower in both the low-dose (p = 0.012 and p = 0.014) and high-dose (p = 0.003 and p = 0.006) meloxicam-treated groups than in the placebo group. In the subchondral bone, only high-dose meloxicam exerted a significant protective effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated animals was abolished in both meloxicam groups. Increase with borderline significance of TNFα in GrpP from week 3 to week 7 (p = 0.049) and reduction of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed.

Conclusion: In this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a chondroprotective effect, and the high dose also protected against subchondral bone lesions. The results suggest a superior protection of the high-dose meloxicam arresting the low-grade inflammatory pathway accompanied by chronic cartilage deterioration.

No MeSH data available.


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Histological findings in the studied groups.(A–C) MIA-induced joint tissue lesions in Grp P. (A) H&E stain, 10x: deformation of the articular surface, cartilage denudation with microfractures (arrow), bone remodeling, and mesenchymal transformation of the bone marrow (arrowhead). (B) H&E stain, 20x: elongated and flattened chondrocytes and extensive zones lacking viable cells (arrow). (C) PAS stain, 10x: superficial zone of cartilage with loss of matrix in the upper one-third (arrow). (D–F) Cartilage and subchondral bone lesions in GrpM Lo. (D) H&E stain, 20x: intact superficial zone with edema and deep fibrillation, disorientation and flattening of the chondrocytes. (E) H&E stain, 10x: erosion with cartilage matrix loss, branched fissure (arrow). (F) H&E stain, 10x: cartilage erosion; vertical, branched fissures (arrow), cysts (arrowhead) and mesenchymal changes affecting up to three-fourths of the bone marrow volume. (G–I) Cartilage and subchondral bone lesions in GrpM Hi. (G) PAS stain, 10x: intact superficial zone, edema, focal matrix condensation (arrow). (H) H&E stain, 10x: disorientation of chondron columns, with cell death, cell clustering and hypertrophy. Bone marrow mesenchymal changes involving approximately one-fourth of the total volume and increased thickening of the subchondral bone marrow. (I) H&E stain, 10x: intact surface with cell death and hypertrophy in the superficial zone, matrix edema, and no marrow changes in the subchondral bone.
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fig-2: Histological findings in the studied groups.(A–C) MIA-induced joint tissue lesions in Grp P. (A) H&E stain, 10x: deformation of the articular surface, cartilage denudation with microfractures (arrow), bone remodeling, and mesenchymal transformation of the bone marrow (arrowhead). (B) H&E stain, 20x: elongated and flattened chondrocytes and extensive zones lacking viable cells (arrow). (C) PAS stain, 10x: superficial zone of cartilage with loss of matrix in the upper one-third (arrow). (D–F) Cartilage and subchondral bone lesions in GrpM Lo. (D) H&E stain, 20x: intact superficial zone with edema and deep fibrillation, disorientation and flattening of the chondrocytes. (E) H&E stain, 10x: erosion with cartilage matrix loss, branched fissure (arrow). (F) H&E stain, 10x: cartilage erosion; vertical, branched fissures (arrow), cysts (arrowhead) and mesenchymal changes affecting up to three-fourths of the bone marrow volume. (G–I) Cartilage and subchondral bone lesions in GrpM Hi. (G) PAS stain, 10x: intact superficial zone, edema, focal matrix condensation (arrow). (H) H&E stain, 10x: disorientation of chondron columns, with cell death, cell clustering and hypertrophy. Bone marrow mesenchymal changes involving approximately one-fourth of the total volume and increased thickening of the subchondral bone marrow. (I) H&E stain, 10x: intact surface with cell death and hypertrophy in the superficial zone, matrix edema, and no marrow changes in the subchondral bone.

Mentions: There were minimal detectable lesions in specimens of GrpCo. In GrpP, tissue lesions were the most severe, with the following key features: erosion, superficial delamination, excavation with matrix loss extending to the mid zone, and denudation with a variable mass of fibrocartilaginous tissue, microfractures of the bone plate. Deformed fibrocartilaginous articular surface was present in one of 11 animals, and severe fragmentation of the calcified cartilage was present in two of 12. Significant (up to ) fibroblastic transformation of the subjacent bone marrow was present in 5 animals (Figs. 2A–2C).


Meloxicam ameliorates the cartilage and subchondral bone deterioration in monoiodoacetate-induced rat osteoarthritis
Histological findings in the studied groups.(A–C) MIA-induced joint tissue lesions in Grp P. (A) H&E stain, 10x: deformation of the articular surface, cartilage denudation with microfractures (arrow), bone remodeling, and mesenchymal transformation of the bone marrow (arrowhead). (B) H&E stain, 20x: elongated and flattened chondrocytes and extensive zones lacking viable cells (arrow). (C) PAS stain, 10x: superficial zone of cartilage with loss of matrix in the upper one-third (arrow). (D–F) Cartilage and subchondral bone lesions in GrpM Lo. (D) H&E stain, 20x: intact superficial zone with edema and deep fibrillation, disorientation and flattening of the chondrocytes. (E) H&E stain, 10x: erosion with cartilage matrix loss, branched fissure (arrow). (F) H&E stain, 10x: cartilage erosion; vertical, branched fissures (arrow), cysts (arrowhead) and mesenchymal changes affecting up to three-fourths of the bone marrow volume. (G–I) Cartilage and subchondral bone lesions in GrpM Hi. (G) PAS stain, 10x: intact superficial zone, edema, focal matrix condensation (arrow). (H) H&E stain, 10x: disorientation of chondron columns, with cell death, cell clustering and hypertrophy. Bone marrow mesenchymal changes involving approximately one-fourth of the total volume and increased thickening of the subchondral bone marrow. (I) H&E stain, 10x: intact surface with cell death and hypertrophy in the superficial zone, matrix edema, and no marrow changes in the subchondral bone.
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fig-2: Histological findings in the studied groups.(A–C) MIA-induced joint tissue lesions in Grp P. (A) H&E stain, 10x: deformation of the articular surface, cartilage denudation with microfractures (arrow), bone remodeling, and mesenchymal transformation of the bone marrow (arrowhead). (B) H&E stain, 20x: elongated and flattened chondrocytes and extensive zones lacking viable cells (arrow). (C) PAS stain, 10x: superficial zone of cartilage with loss of matrix in the upper one-third (arrow). (D–F) Cartilage and subchondral bone lesions in GrpM Lo. (D) H&E stain, 20x: intact superficial zone with edema and deep fibrillation, disorientation and flattening of the chondrocytes. (E) H&E stain, 10x: erosion with cartilage matrix loss, branched fissure (arrow). (F) H&E stain, 10x: cartilage erosion; vertical, branched fissures (arrow), cysts (arrowhead) and mesenchymal changes affecting up to three-fourths of the bone marrow volume. (G–I) Cartilage and subchondral bone lesions in GrpM Hi. (G) PAS stain, 10x: intact superficial zone, edema, focal matrix condensation (arrow). (H) H&E stain, 10x: disorientation of chondron columns, with cell death, cell clustering and hypertrophy. Bone marrow mesenchymal changes involving approximately one-fourth of the total volume and increased thickening of the subchondral bone marrow. (I) H&E stain, 10x: intact surface with cell death and hypertrophy in the superficial zone, matrix edema, and no marrow changes in the subchondral bone.
Mentions: There were minimal detectable lesions in specimens of GrpCo. In GrpP, tissue lesions were the most severe, with the following key features: erosion, superficial delamination, excavation with matrix loss extending to the mid zone, and denudation with a variable mass of fibrocartilaginous tissue, microfractures of the bone plate. Deformed fibrocartilaginous articular surface was present in one of 11 animals, and severe fragmentation of the calcified cartilage was present in two of 12. Significant (up to ) fibroblastic transformation of the subjacent bone marrow was present in 5 animals (Figs. 2A–2C).

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Objective: This study aimed to quantify the cartilage- and subchondral bone-related effects of low-dose and high-dose meloxicam treatment in the late phase of mono-iodoacetate-induced osteoarthritis of the stifle.

Methods: Thirty-four male Wistar rats received intra-articular injection of mono-iodoacetate to trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono-iodoacetate-injected rats were assigned to three groups and treated from week 4 to the end of week 7 with placebo (Grp P, n = 11), low-dose (GrpM Lo, 0.2 mg/kg, n = 12) or high-dose (GrpM Hi, 1 mg/kg, n = 11) meloxicam. After a period of 4 additional weeks (end of week 11) the animals were sacrificed, and the stifle joints were examined histologically and immunohistochemically for cyclooxygenase 2, in conformity with recommendations of the Osteoarthritis Research Society International. Serum cytokines IL-6, TNFα and IL-10 were measured at the end of weeks 3, 7, and 11.

Results: Compared with saline-treated controls, animals treated with mono-iodoacetate developed various degrees of osteoarthritis. The cartilage degeneration score and the total cartilage degeneration width were significantly lower in both the low-dose (p = 0.012 and p = 0.014) and high-dose (p = 0.003 and p = 0.006) meloxicam-treated groups than in the placebo group. In the subchondral bone, only high-dose meloxicam exerted a significant protective effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated animals was abolished in both meloxicam groups. Increase with borderline significance of TNFα in GrpP from week 3 to week 7 (p = 0.049) and reduction of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed.

Conclusion: In this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a chondroprotective effect, and the high dose also protected against subchondral bone lesions. The results suggest a superior protection of the high-dose meloxicam arresting the low-grade inflammatory pathway accompanied by chronic cartilage deterioration.

No MeSH data available.


Related in: MedlinePlus