Comparison Of Human Articular Cartilage Tissue And Chondrocytes Isolated From Peripheral vs Central Regions Of Traumatic Lesions

Background. It is generally assumed that traumatic cartilage lesions affect the whole joint homeostasis. However, it remains unknown to which extent the properties of chondrocytes within lesions are affected compared to cells from adjacent locations. To unravel cellular and molecular events occurring in cartilage regions close to injury sites, we collected cartilage biopsies from the central part of the lesions ( central ) and from regions closely surrounding the lesion ( peripheral , 2-5mm distance from defect) of traumatic joints and assessed their key functional properties. Additionally, we investigated the correlation of these properties with the inflammatory features of the joint and the quality of the initial cartilage biopsy. Methods. Cartilage samples were collected from the knee joints of 42 patients (male:female = 7:3, age range: 18-60y) with traumatic knee injuries and analysed for cell phenotype (by RT-PCR), histological quality (using a grading score based on glycosaminoglycan staining), cellularity (cell numbers/gram tissue, isolated after enzymatic digestion), cell viability, proliferation capacity (cell doublings/day) and post-expansion chondrogenic capacity of chondrocytes (Bern score of chondrogenically cultured cells in pellets). In addition, synovial tissues were harvested and analysed for the expression of inflammatory cytokine genes. Results. Cartilage quality and post-expansion chondrogenic capacity were higher in peripheral vs central samples. Differences between these two parameters were more pronounced in joints with high (vs low) inflammatory features, as characterised by >100-fold difference in the mRNA levels of IL-6 and IL-8 in the corresponding synovial tissues. Peripheral chondrocytes isolated from initially good compared to bad quality biopsies expressed higher levels of chondrogenic markers (type II/I collagen and aggrecan/versican ratios) and lower levels of cartilage degrading markers MMP13 and ADAMTS5. They also exhibited reduced proliferation and enhanced cartilage-forming capacity. Conclusions. Chondrocytes at the periphery of traumatic lesions better maintain properties typical of healthy cartilage as compared to those isolated from central parts even when derived from bad quality tissues harvested from highly inflamed joints. Future studies will be necessary to investigate the change of functional properties of peripheral chondrocytes over time and, consequently, to identify a “point of no return” (since onset of symptoms) for a possible use of such chondrocytes in cartilage repair strategies.