期刊
OSTEOARTHRITIS AND CARTILAGE
卷 24, 期 10, 页码 1786-1794出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2016.05.019
关键词
Osteoarthritis; Cartilage; Ion channels; ACLT; Chloride channel; Anion channel; Caspase; Apoptosis
资金
- Japan Society for the Promotion of Science (JSPS) [26861185]
- UK Royal Society [IE140240]
- Gen Foundation
- Grants-in-Aid for Scientific Research [26861185] Funding Source: KAKEN
Objective: The anterior cruciate ligament transection (ACLT) rabbit osteoarthritis (OA) model confers permanent knee instability and induces joint degeneration. The degeneration process is complex, but includes chondrocyte apoptosis and OA-like loss of cartilage integrity. Previously, we reported that activation of a volume-sensitive Cl- current (ICl, vol) can mediate cell shrinkage and apoptosis in rabbit articular chondrocytes. Our objective was therefore to investigate whether ICl, vol was activated in the early stages of the rabbit ACLT OA model. Design: Adult Rabbits underwent unilateral ACLT and contralateral arthrotomy (sham) surgery. Rabbits were euthanized at 2 or 4 weeks. Samples were analyzed histologically and with assays of cell volume, apoptosis and electrophysiological characterization of ICl, vol. Results: At 2 and 4 weeks post ACLT cartilage appeared histologically normal, nevertheless cell swelling and caspase 3/7 activity were both significantly increased compared to sham controls. In cell-volume experiments, exposure of chondrocytes to hypotonic solution led to a greater increase in cell size in ACLT compared to controls. Caspase-3/7 activity, an indicator of apoptosis, was elevated in both ACLT 2wk and 4wk. Whole-cell currents were recorded with patch clamp of chondrocytes in iso-osmotic and hypo-osmotic external solutions under conditions where Na+, K+ and Ca2+ currents were minimized. ACLT treatment resulted in a large increase in hypotonic-activated chloride conductance. Conclusion: Changes in chondrocyte ion channels take place prior to the onset of apparent cartilage loss in the ACLT rabbit model of OA. Further studies are needed to investigate if pharmacological inhibition of ICl, vol decreases progression of OA in animal models. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
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