An In Vitro System to Study the Effect of Subchondral Bone Health on Articular Cartilage Repair in Humans.

Timothy Hopkins,Peter Gallacher,Sally Roberts,Paul Jermin,Karina T Wright,Jan Herman Kuiper,Nicola J Kuiper

doi:10.3390/cells10081903

Timothy Hopkins, Peter Gallacher + Show 5 more

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https://doi.org/10.3390/cells10081903

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Abstract

Chondrocyte-based cartilage repair strategies, such as articular chondrocyte implantation, are widely used, but few studies addressed the communication between native subchondral bone cells and the transplanted chondrocytes. An indirect co-culture model was developed, representing a chondrocyte/scaffold-construct repair of a cartilage defect adjoining bone, where the bone could have varying degrees of degeneration. Human BM-MSCs were isolated from two areas of subchondral bone in each of five osteochondral tissue specimens from five patients undergoing knee arthroplasty. These two areas underlaid the macroscopically and histologically best and worst cartilage, representing early and late-stage OA, respectively. 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, and the abundance of selected proteins in conditioned media was assessed by ELISA. Co-culture with late-OA BM-MSCs resulted in a reduction in GAG deposition and a decreased expression of genes encoding matrix-specific proteins (COL2A1 and ACAN), compared to culturing with early OA BM-MSCs. The concentration of TGF-β1 was significantly higher in the early OA conditioned media. The results of this study have clinical implications for cartilage repair, suggesting that the health of the subchondral bone may influence the outcomes of chondrocyte-based repair strategies.

Highlights

In the human knee, the articular cartilage (AC) forms a complex, biomechanically functional unit with the subchondral bone (SB), the osteochondral unit, in which the components act together to dissipate forces generated during articulation [1]
The tissue that demonstrated the best and worst International Cartilage Repair Society (ICRS) grade were collected from each patient, resulting in 10 tissue segments in total from total knee replacement (TKR) patients
Xu and colleagues reported that indirect co-culture of rabbit articular chondrocytes with rabbit MSCs reduced proliferation of chondrocytes and production of cartilage ECM proteins, including GAGs, compared to monoculture of articular chondrocytes, and that this effect was mediated entirely via secreted factors [42]

Summary

Introduction

The articular cartilage (AC) forms a complex, biomechanically functional unit with the subchondral bone (SB), the osteochondral unit, in which the components act together to dissipate forces generated during articulation [1]. The osteochondral unit can be considered a biochemically and biomechanically functional unit, and processes that disrupt homeostasis in either tissue will alter the properties and function of the other [1,3,4]. This is reflected in osteoarthritis (OA) pathogenesis, in which SB thickening and AC degradation are two of the most common features, and pathological changes in the SB often parallel those seen in the overlying AC [12,13]. Little consideration is given to the health status of the SB in influencing the outcomes of cell-based strategies for AC repair, which are widely used in the treatment of early degenerative or traumatic lesions

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