Abstract
Abstract
Objectives
Human articular cartilage chondrocytes undergo changes to their morphology and clustering with cartilage degeneration as occurs in osteoarthritis(1). The consequences of chondrocyte de-differentiation on mechanically-resilient extracellular matrix metabolism are, however, unclear. We have assessed whether there is a relationship between abnormal chondrocyte morphology, as demonstrated by the presence of cytoplasmic processes, and chondrocyte clustering, with cell-associated type-I collagen during cartilage degeneration.
Methods
The femoral heads of 9 patients were obtained (with Ethical permission/consent) following hip replacement surgery and cartilage areas graded (Grade-0 non-degenerate; Grade-1 mildly degenerate). In situ chondrocyte morphology and cell-associated type-I collagen were labelled fluorescently with CMFDA Cell tracker green, and immuno-fluorescence respectively then visualised/quantified using confocal laser scanning microscopy and imaging software.
Results
When comparing data from 9 femoral heads with Grade-0 [N(n)=6(72)] or Grade-1 cartilage [(N(n)=9(108)], the latter had a higher percentage of chondrocytes with cytoplasmic processes (length >5µm) (P=0.018) and clusters (≥5 cells within a lacuna) (P<0.001). The percentage of chondrocytes with processes and clusters displaying cell-associated type-I collagen, was also higher in degenerate cartilage (P<0.001 for both). However, some morphologically-normal chondrocytes exhibited cell-associated collagen type-I labelling while some clusters did not label with collagen type-I. Intriguingly, even in Grade-0 cartilage, some chondrocytes were morphologically abnormal and exhibited cell-associated type-I collagen.
Conclusions
These results suggest a complex relationship between chondrocyte morphology/clusters and cell-associated collagen type-I. The presence of this collagen type implies chondrocyte de-differentiation to a fibroblastic phenotype even in non-degenerate cartilage. This cell type produces a fibro-cartilaginous ‘repair’ matrix which is considerably weaker than the collagen type-II matrix of healthy hyaline cartilage and may give rise to focal points of mechanical weakness.
Funder
Chief Scientist's Office, Scotland (Grant TCS/18/01).
Declaration of Interest
(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
