Background/Purpose: Terminal differentiating growth plate chondrocytes are mainly characterized by an increase of their cell size and by the expression of hypertrophic markers such as type X Collagen. Likely, during osteoarthritis (OA) progression, articular chondrocytes acquire a similar protein profile, and, therefore, they have been commonly described as hypertrophic-like chondrocytes. Our aim was to study whether an increase in chondrocyte size may be a feature of the hypertrophic-like phenotype in the articular cartilage (AC) of experimental OA rabbits and in OA human cartilage. The anatomical location of these bigger cells in the deeper zones was also assessed.

Methods:

New Zealand female rabbits were randomly assigned to four groups: healthy (n=8), osteoporosis (OP, n=7), OA (n=8) and OA preceded by OP (OPOA, n=8). OP was induced by ovariectomy followed by metilprednisolone administration (1mg/kg/day) during four weeks. OA was induced by anterior cruciate ligament section and partial medial meniscectomy, lasting over a period of 6 weeks. All animals were euthanized and tibias were collected for histological analysis. Cartilage damage and chondrocyte size were assessed in Safranin-O fast green stained sections. Type X Collagen presence was analyzed by immunohistochemistry. Nine human samples were obtained during total knee replacement surgery to perform identical histological studies after the informed consent was gained. Statistical comparisons were performed using Kruskal-Wallis and Mann Whitney tests, whereas correlations were done with Spearman test.

Results:

Mankin score showed an increase in cartilage damage in all groups in comparison to healthy rabbits. The most severe cartilage damage was observed in the OPOA group (Healthy: 1.0 (0-1.5), OP: 2.3 (1.5-4.5), OA: 8.0 (7-13), OPOA: 13 (11-16)). Chondrocyte size in OA and OPOA cartilages were greater than that in healthy cartilage, and significantly greater in OPOA vs OA (Healthy: 133.0 (91.1-158.7), OP: 140.7 (119.7-198.3), OA: 180.9 (120.5-266.4), OPOA: 217.4 (183.6-303.5). However, no differences in the mean chondrocyte size were found between the deepest and in the most superficial regions of the AC in any of the groups analyzed. Chondrocyte size and cartilage damage were significantly and positively correlated (p<0.001, r=0.718). In addition, chondrocyte size was also associated with immunoreactive type X Collagen staining (p<0.05, r=0.444). Regarding human OA cartilage, chondrocyte size also correlated with cartilage damage and with type X Collagen presence (p<0.001, r=0.921 and p<0.05, r=0.663 respectively).

Conclusion: We observed an increase of the chondrocyte size in OA cartilage in relation to an increased cartilage damage. These bigger chondrocytes were homogeneously distributed in the deepest and in the most superficial regions of the AC. A positive correlation was also found between the chondrocyte size and the presence of type X Collagen, both in human and experimental OA cartilage. Our results suggest that chondrocyte size could be a reliable hypertrophic marker of the OA articular cartilage.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/chondrocyte-size-in-articular-cartilage-as-a-marker-of-osteoarthritis-severity/