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Research

AN IN VITRO SYSTEM TO STUDY THE EFFECT OF SUBCHONDRAL BONE HEALTH ON ARTICULAR CARTILAGE REPAIR IN HUMANS

The British Orthopaedic Research Society (BORS) Annual Meeting 2021, held online, 13–14 September 2021.



Abstract

Abstract

Objectives

In the human knee, the cells of the articular cartilage (AC) and subchondral bone (SB) communicate via the secretion of biochemical factors. Chondrocyte-based AC repair strategies, such as articular chondrocyte implantation, are widely used but there has been little investigation into the communication between the native SB cells and the transplanted chondrocytes. We hypothesise that this communication depends on the health state of the SB and could influence the composition and quality of the repair cartilage.

Methods

An indirect co-culture model was developed using transwell inserts, representing a chondrocyte/scaffold-construct for repair of AC defects adjoining SB with varying degrees of degeneration. Donor-matched populations of human bone-marrow derived mesenchymal stromal cells (BM-MSCs) were isolated from the macroscopically and histologically best and worst osteochondral tissue, representing “healthy” and “unhealthy” SB. The BM-MSCs were co-cultured with normal chondrocytes suspended in agarose, with the two cell types separated by a porous membrane. After 0, 7, 14 and 21 days, chondrocyte-agarose scaffolds were assessed by gene expression and biochemical analyses.

Results

Matched healthy and unhealthy BM-MSCs from five patients undergoing knee arthroplasty (2 male, 3 female; 72.8±2.2SD years-old) were used, together with normal chondrocytes from a healthy patient (male; 24 years-old). At day 21, there was significantly more glycosaminoglycan per chondrocyte in the scaffolds co-cultured with healthy BM-MSCs (4.37×10−4μg/cell±2.69×10−5SEM) than in those cultured with unhealthy BM-MSCs (3.52×10−4μg/cell±2.19×10−5SEM; p<0.001). Co-culture with unhealthy BM-MSCs caused a difference in expression of COL2A1 (day 0–21 fold change; unhealthy:-32.8±12.9SEM; healthy:-7.82±4.46SEM; p<0.001) and ACAN (unhealthy:+1.51±0.51SEM; healthy:+4.05±0.49SEM; p=0.002).

Conclusions

Co-culture with unhealthy BM-MSCs caused a reduction in GAG deposition and expression of genes encoding matrix-specific proteins, compared to culturing with healthy BM-MSCs. There are clinical implications for cell-based cartilage repair, where the health of the SB may influence the outcome of chondrocyte-based therapies.