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.
Highlights
Chondrocyte death is a known feature of osteoarthritis (OA)
There is a need for longitudinal studies of suitable animal models of OA to clarify the role of chondrocyte apoptosis in the pathogenesis of OA
Articular cartilage surface (ACS) score was higher in the Dunkin Hartley (DH) strain than Bristol strain 2 (BS2) at all time points in both medial and lateral (Figure 2A), but reached statistical significance only in the lateral side of AC at weeks
Summary
Chondrocyte death is a known feature of osteoarthritis (OA). It has been hypothesised as a key player in the pathogenesis of OA based on the presence of hypocellularity and a large number of empty lacunae, especially in regions close to fibrillated areas of osteoarthritic cartilage [1,2]. Chondrocyte apoptosis can be induced by exposing the normal cartilage explants or chondrocyte cultures either to biological [14,19,24] (e.g., nitric oxide (NO), collagenase, anti-CD95) or mechanical factors [10,11,25,26] (e.g., shear strain, loading strain) This effect can be inhibited by treatment with caspase inhibitor [24,27,28] (e.g., z.VAD.fmk), Insulin-like growth factor 1 (IGF-1) [24], N-acetylcysteine (NAC) [29] and p38 MAPK inhibitor [14].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
