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The repair of articular cartilage typically involves the repair of cartilage–subchondral bone tissue defects. Although various bioactive materials have been used to repair bone defects, how these bioactive materials in subchondral bone defects influence the repair of autologous cartilage transplant remains unclear. The aim of this study was to investigate the effects of different subchondral biomaterial scaffolds on the repair of autologous cartilage transplant in a sheep model. Cylindrical cartilage–subchondral bone defects were created in the right femoral knee joint of each sheep. The subchondral bone defects were implanted with hydroxyapatite–β-tricalcium phosphate (HA–TCP), poly lactic-glycolic acid (PLGA)-HA–TCP dual-layered composite scaffolds (PLGA/HA–TCP scaffolds), or autologous bone chips. The autologous cartilage layer was placed on top of the subchondral materials. After 3 months, the effect of different subchondral scaffolds on the repair of autologous cartilage transplant was systematically studied by investigating the mechanical strength, structural integration, and histological responses. The results showed that the transplanted cartilage layer supported by HA–TCP scaffolds had better structural integration and higher mechanical strength than that supported by PLGA/HA–TCP scaffolds. Furthermore, HA–TCP-supported cartilage showed higher expression of acid mucosubstances and glycol-amino-glycan contents than that supported by PLGA/HA–TCP scaffolds. Our results suggested that the physicochemical properties, including the inherent mechanical strength and material chemistry of the scaffolds, play important roles in influencing the repair of autologous cartilage transplants. The study may provide useful information for the design and selection of proper subchondral biomaterials to support the repair of both subchondral bone and cartilage defects. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Relative indentation characteristics are commonly used for distinguishing between normal healthy and degraded cartilage. The application of this parameter in surgical decision making and an appreciation of articular cartilage biomechanics has prompted us to hypothesise that it is difficult to define a reference stiffness to characterise normal articular cartilage. Methods: This hypothesis is tested for validity by carrying out biomechanical indentation of articular cartilage samples that are characterised as visually normal and degraded relative to proteoglycan depletion and collagen disruption. Compressive loading was applied at known strain rates to visually normal, artificially degraded and naturally osteoarthritic articular cartilage and observing the trends of their stress–strain and stiffness characteristics. Findings: While our results demonstrated a 25% depreciation in the stiffness of individual samples after proteoglycan depletion, they also showed that when compared to the stiffness of normal samples only 17% lie outside the range of the stress–strain behaviour of normal samples. Interpretation: We conclude that the extent of the variability in the properties of normal samples, and the degree of overlap (81%) of the biomechanical properties of normal and degraded matrices demonstrate that indentation data cannot form an accurate basis for distinguishing normal from abnormal articular cartilage samples with consequences for the application of this mechanical process in the clinical environment. [Copyright &y& Elsevier]

Altered subchondral bone and articular cartilage interactions have been implicated in the pathogenesis of osteoarthritis (OA); however, the mechanisms remain unknown. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication. Herein, we investigated if OA subchondral bone derived exosomes alter transcriptional and bioenergetic signatures of chondrocytes. Exosomes were isolated and purified from osteoblasts of nonsclerotic or sclerotic zones of human OA subchondral bone and their role on the articular cartilage chondrocytes was evaluated by measuring the extent of extracellular matrix production, cellular bioenergetics, and the expression of chondrocyte activity associated marker genes. Exosomal microRNAs were analyzed using RNA sequencing and validated by quantitative real-time PCR and loss-of-function. In coculture studies, chondrocytes internalized OA sclerotic subchondral bone osteoblast derived exosomes and triggered catabolic gene expression and reduced chondrocyte-specific marker expression a phenomenon that is often observed in OA cartilage. RNA sequencing and miRNA profiling have identified miR-210-5p, which is highly enriched in OA sclerotic subchondral bone osteoblast exosomes, triggered the catabolic gene expression in articular cartilage chondrocytes. Importantly, we demonstrate that miR-210-5p suppresses the oxygen consumption rate of chondrocytes, altering their bioenergetic state that is often observed in OA conditions. These effects were markedly inhibited by the addition of a miR-210-5p inhibitor. Our study indicates that exosomes released by OA sclerotic subchondral bone osteoblasts plays a critical role in progression of cartilage degeneration and might be a potential target for therapeutic intervention in OA. [ABSTRACT FROM AUTHOR]