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Increased chondrocyte apoptosis is associated with progression of osteoarthritis in spontaneous Guinea pig models of the disease.

Zamli Z, Adams MA, Tarlton JF, Sharif M - Int J Mol Sci (2013)

Bottom Line: DH had a significant progression of chondrocyte death between 24 to 30 weeks during which time significant changes were observed in AC fibrillation, proteoglycan depletion and overall microscopic OA score.A strong correlation (p ≤ 0.01) was found between chondrocyte apoptosis and AC fibrillation (r = 0.3), cellularity (r = 0.4) and overall microscopic OA scores (r = 0.4).Overall, the rate of progression in OA and apoptosis over the study period was greater in the DH (versus BS2) and the medial AC (versus lateral).

View Article: PubMed Central - PubMed

Affiliation: Centre for Comparative and Clinical Anatomy, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK.

ABSTRACT
Osteoarthritis (OA) is the most common joint disease characterised by degradation of articular cartilage and bone remodelling. For almost a decade chondrocyte apoptosis has been investigated as a possible mechanism of cartilage damage in OA, but its precise role in initiation and/or progression of OA remains to the determined. The aim of this study is to determine the role of chondrocyte apoptosis in spontaneous animal models of OA. Right tibias from six male Dunkin Hartley (DH) and Bristol Strain 2 (BS2) guinea pigs were collected at 10, 16, 24 and 30 weeks of age. Fresh-frozen sections of tibial epiphysis were microscopically scored for OA, and immunostained with caspase-3 and TUNEL for apoptotic chondrocytes. The DH strain had more pronounced cartilage damage than BS2, especially at 30 weeks. At this time point, the apoptotic chondrocytes were largely confined to the deep zone of articular cartilage (AC) with a greater percentage in the medial side of DH than BS2 (DH: 5.7%, 95% CI: 4.2-7.2), BS2: 4.8%, 95% CI: 3.8-5.8), p > 0.05). DH had a significant progression of chondrocyte death between 24 to 30 weeks during which time significant changes were observed in AC fibrillation, proteoglycan depletion and overall microscopic OA score. A strong correlation (p ≤ 0.01) was found between chondrocyte apoptosis and AC fibrillation (r = 0.3), cellularity (r = 0.4) and overall microscopic OA scores (r = 0.4). Overall, the rate of progression in OA and apoptosis over the study period was greater in the DH (versus BS2) and the medial AC (versus lateral). Chondrocyte apoptosis was higher at the later stage of OA development when the cartilage matrix was hypocellular and highly fibrillated, suggesting that chondrocyte apoptosis is a late event in OA.

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Percentage of caspase-3 positive chondrocytes in the medial and lateral side of AC in DH (n = 6) and BS2 (n = 6) at four different time points. Error bars represent the 95% CI.
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f4-ijms-14-17729: Percentage of caspase-3 positive chondrocytes in the medial and lateral side of AC in DH (n = 6) and BS2 (n = 6) at four different time points. Error bars represent the 95% CI.

Mentions: The percentage of caspase-3 positive chondrocytes was always higher in the medial (DH: 2.9% (95% CI: 2.0–3.7); BS2: 3.1% (95% CI: 2.4–3.8)) than the lateral side (DH: 1.8% (95% CI: 1.3–2.3); BS2: 2.4% (95% CI: 1.9–2.9)) and increases gradually over time in both strains (Figure 4). In the medial side, BS2 showed a slightly higher percentage of chondrocyte apoptosis than DH for the earlier time points, but the rate of increase of apoptotic cells was greater in the DH such that at 30 weeks, the DH was greater than the BS2 [DH: 5.7% (95% CI: 4.2–7.2), BS2: 4.8% (95% CI: 3.8–5.8), p > 0.05]. Though the increase in apoptotic chondrocytes was apparent with increasing age, it was only in the medial side of the DH AC between 24 and 30 weeks that this was significant (p ≤ 0.01). A significant difference between strains at a particular time point is only seen in the lateral side of AC at 10 weeks (p ≤ 0.01), with the BS2 greater than the DH.


Increased chondrocyte apoptosis is associated with progression of osteoarthritis in spontaneous Guinea pig models of the disease.

Zamli Z, Adams MA, Tarlton JF, Sharif M - Int J Mol Sci (2013)

Percentage of caspase-3 positive chondrocytes in the medial and lateral side of AC in DH (n = 6) and BS2 (n = 6) at four different time points. Error bars represent the 95% CI.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3794750&req=5

f4-ijms-14-17729: Percentage of caspase-3 positive chondrocytes in the medial and lateral side of AC in DH (n = 6) and BS2 (n = 6) at four different time points. Error bars represent the 95% CI.
Mentions: The percentage of caspase-3 positive chondrocytes was always higher in the medial (DH: 2.9% (95% CI: 2.0–3.7); BS2: 3.1% (95% CI: 2.4–3.8)) than the lateral side (DH: 1.8% (95% CI: 1.3–2.3); BS2: 2.4% (95% CI: 1.9–2.9)) and increases gradually over time in both strains (Figure 4). In the medial side, BS2 showed a slightly higher percentage of chondrocyte apoptosis than DH for the earlier time points, but the rate of increase of apoptotic cells was greater in the DH such that at 30 weeks, the DH was greater than the BS2 [DH: 5.7% (95% CI: 4.2–7.2), BS2: 4.8% (95% CI: 3.8–5.8), p > 0.05]. Though the increase in apoptotic chondrocytes was apparent with increasing age, it was only in the medial side of the DH AC between 24 and 30 weeks that this was significant (p ≤ 0.01). A significant difference between strains at a particular time point is only seen in the lateral side of AC at 10 weeks (p ≤ 0.01), with the BS2 greater than the DH.

Bottom Line: DH had a significant progression of chondrocyte death between 24 to 30 weeks during which time significant changes were observed in AC fibrillation, proteoglycan depletion and overall microscopic OA score.A strong correlation (p ≤ 0.01) was found between chondrocyte apoptosis and AC fibrillation (r = 0.3), cellularity (r = 0.4) and overall microscopic OA scores (r = 0.4).Overall, the rate of progression in OA and apoptosis over the study period was greater in the DH (versus BS2) and the medial AC (versus lateral).

View Article: PubMed Central - PubMed

Affiliation: Centre for Comparative and Clinical Anatomy, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK.

ABSTRACT
Osteoarthritis (OA) is the most common joint disease characterised by degradation of articular cartilage and bone remodelling. For almost a decade chondrocyte apoptosis has been investigated as a possible mechanism of cartilage damage in OA, but its precise role in initiation and/or progression of OA remains to the determined. The aim of this study is to determine the role of chondrocyte apoptosis in spontaneous animal models of OA. Right tibias from six male Dunkin Hartley (DH) and Bristol Strain 2 (BS2) guinea pigs were collected at 10, 16, 24 and 30 weeks of age. Fresh-frozen sections of tibial epiphysis were microscopically scored for OA, and immunostained with caspase-3 and TUNEL for apoptotic chondrocytes. The DH strain had more pronounced cartilage damage than BS2, especially at 30 weeks. At this time point, the apoptotic chondrocytes were largely confined to the deep zone of articular cartilage (AC) with a greater percentage in the medial side of DH than BS2 (DH: 5.7%, 95% CI: 4.2-7.2), BS2: 4.8%, 95% CI: 3.8-5.8), p > 0.05). DH had a significant progression of chondrocyte death between 24 to 30 weeks during which time significant changes were observed in AC fibrillation, proteoglycan depletion and overall microscopic OA score. A strong correlation (p ≤ 0.01) was found between chondrocyte apoptosis and AC fibrillation (r = 0.3), cellularity (r = 0.4) and overall microscopic OA scores (r = 0.4). Overall, the rate of progression in OA and apoptosis over the study period was greater in the DH (versus BS2) and the medial AC (versus lateral). Chondrocyte apoptosis was higher at the later stage of OA development when the cartilage matrix was hypocellular and highly fibrillated, suggesting that chondrocyte apoptosis is a late event in OA.

Show MeSH
Related in: MedlinePlus