Proliferative remodeling of the spatial organization of human superficial chondrocytes distant from focal early osteoarthritis

Objective—Human superficial chondrocytes show distinct spatial organizations whereas they commonly aggregate near osteoarthritic (OA) fissures. It is not known whether remodeling or destruction of the spatial chondrocyte organization may occur distant to focal (early) OA lesions. Methods—The intact cartilages (condyles, patellofemoral groove, proximal tibia) distant to focal OA lesions of human grade 2 joints were compared to location-matched non-degenerative (grade 0–1) cartilages. Chondrocyte nuclei were stained with propidium iodide and recorded by fluorescence-microscopy in a top-down view. Chondrocyte arrangements were tested for randomness or significant grouping via point pattern analyses (Clark and Evans Aggregation Index), and were correlated with OA grade and surface cell densities. Results—In grade 2 cartilages, superficial chondrocytes were situated in horizontal patterns such as strings, cluster, pairs and singles comparable to non-degenerative cartilage. In the intact cartilages of grade 2 joints, the spatial organization included a novel pattern, consisting of chondrocytes that were aligned in two parallel lines building double strings. These double strings correlated with an increased number of chondrocytes per group (p<0.05), increased corresponding superficial zone cell density (p<0.001), and were observed in all grade 2 condyles (p<0.001), some grade 2 tibiae (p<0.05) but never in grade 0–1 cartilage (p<0.001). Conclusion—The present study is the first to identify a distinct spatial re-organization of human superficial chondrocytes in response to distant early OA lesions and suggests that proliferation had occurred distant to focal early OA. This spatial re-organization may serve to recruit metabolically active units as attempt to repair focal damage.