Abnormal human chondrocyte morphology is related to increased levels of cell-associated IL-1 beta and disruption to pericellular collagen yype VI

D.H. Murray, Peter Bush, I.J. Brenkel, A.C. Hall

Research output: Contribution to journalArticle

Abstract

Early osteoarthritis (OA) is poorly understood, but abnormal chondrocyte morphology might be important. We studied IL-1β and pericellular collagen type VI in morphologically normal and abnormal chondrocytes. In situ chondrocytes within explants from nondegenerate (grade 0/1) areas of human tibial plateaus (n = 21) were fluorescently labeled and visualized [2-photon laser scanning microscopy (2PLSM)]. Normal chondrocytes exhibited a "smooth" membrane surface, whereas abnormal cells were defined as demonstrating ≥1 cytoplasmic process. Abnormal chondrocytes were further classified by number and average length of cytoplasmic processes/cell. IL-1β or collagen type VI associated with single chondrocytes were visualized by fluorescence immuno-histochemistry and confocal laser scanning microscopy (CLSM). Fluorescence was quantified as the number of positive voxels (i.e., 3D pixels with fluorescence above baseline)/cell. IL-1β-associated fluorescence increased between normal and all abnormal cells in the superficial (99.7 ± 29.8 [11 (72)] vs. 784 ± 382 [15 (132)]; p = 0.04, positive voxels/cell) and deep zones (66.5 ± 29.4 [9 (64)] vs. 795 ± 224 [9 (56)]; p = 0.006). There was a correlation (r(2) = 0.988) between the number of processes/cell (0-5) and IL-1β, and an increase particularly with short processes (≤5 µm; p = 0.022). Collagen type VI coverage and thickness decreased (p < 0.001 and p = 0.005, respectively) with development of processes. Abnormal chondrocytes in macroscopically nondegenerate cartilage demonstrated a marked increase in IL-1β and loss of pericellular type VI collagen, changes that could lead to cartilage degeneration.
Original languageEnglish
Pages (from-to)1507-1514
Number of pages8
JournalJournal of Orthopaedic Research
Volume28
Issue number11
DOIs
Publication statusPublished - 30 Nov 2010

Bibliographical note

© 2010 Orthopaedic Research Society

Keywords

  • osteoarthritis
  • chondrocyte
  • collagen type VI
  • interleukin
  • morphology

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