Chondrocyte clusters adjacent to sites of cartilage degeneration have characteristics of progenitor cells

Abstract

The purpose of this study was to investigate the site-specific expression pattern and the role of chondrocyte clusters in human OA knee. Cartilage explants were obtained from 45 varus knees of medial and lateral femoral condyle undergoing total knee replacement surgery. Cartilage degeneration, number of chondrocytes, and the cell arrangement were evaluated by live/dead assay and immunohistochemical analyses with antibodies of STRO-1, FGF2, and Ki-67. Chondrocytes from medial and lateral femoral condyle were cultured to compare the potential of cell proliferation and production of cartilaginous nodules. Finally, cartilage tissue from medial femoral condyle, which included cartilage cleft with chondrocyte clusters, was observed the histological alternation. As the results, chondrocyte density adjacent to severe cartilage degeneration was highest, whereas chondrocytes in lateral femoral condyle displayed low density with single type of cells. Over 80% of these chondrocyte clusters were survived, expressing STRO-1, FGF2, and Ki-67. Furthermore, chondrocyte clusters proliferated faster and produced more cartilaginous nodules than single type of chondrocytes. Cartilage clefts involving numerous chondrocyte clusters were filled with extracellular matrix during organ culture. In conclusion, chondrocyte clusters adjacent to severe cartilage degeneration have shown completely specific characteristics with progenitor and proliferative potential. Regulating chondrocyte clusters may offer new approaches to cartilage repair and OA therapy in the future.

Histopathological assessment of primary osteoarthritic knees in large patient cohort reveal the possibility of several potential patterns of osteoarthritis initiation

“…[24] Second, hypercellularity was scored based on the prevalence of doublets/triplets along the width of the hyaline cartilage[25] and distinguished from cloning by a 6-cell cluster cutoff. [26] Third, a cloning score did not consider cell numbers sharing the same territorial matrix above the cutoff, nor did it consider a single clonal unit distinct from several clonal units. Fourth, SafO-FG staining reduction was assessed as the percentage of total tissue area devoid of stain: slight <33%, moderate 33–66% and severe 66–99%.…”

Ageing and the pathogenesis of osteoarthritis

“…For example, bFGF is released from damaged cartilage tissue 49 , and can be detected in focal clusters of chondrocyte proliferation that develop near areas of cartilage damage 50 . As a downstream result of signalling by inflammatory cytokines associated with OA, expression of bone morphogenetic protein 2 (BMP-2) is increased, 51 thereby stimulating enhanced turnover of extracellular matrix 52 .…”

Effect of Laminin‐A4 inhibition on cluster formation of human osteoarthritic chondrocytes

“…These clusters are a typical histological feature in OA . Chondrocyte clusters adjacent to severe cartilage degeneration have specific progenitor and proliferative potential . Yet the aggregation of hypertrophic chondrocytes could also be caused by locomotory activity, which has been shown to occur in cell culture models using e.g.…”

“…Yet the aggregation of hypertrophic chondrocytes could also be caused by locomotory activity, which has been shown to occur in cell culture models using e.g. collagen enriched hydrogel matrices …”

“…collagen enriched hydrogel matrices. [7][8][9] Locomotion of cells is dependent on adhesion molecules and integrin expression. Integrins regulate the proliferation, migration, survival, and differentiation of chondrocytes.…”