A type VI collagen-rich pericellular matrix (PCM) encloses both intervertebral disk (IVD) and articular cartilage chondrocytes. In the latter, the PCM protects the chondrocytes from mechanical overload, whereas tissue degeneration is associated with PCM destruction. As little is known about the IVD PCM, we investigated chondrocyte survival after mechanical overload as well as PCM structural integrity as a function of clinical tissue degeneration. The hypothesis was that IVD degeneration may affect PCM integrity and overload-related chondrocyte survival. Cylindrical human IVD explants from patients undergoing surgical procedures for lumbar disk degeneration, disk prolapse, or spinal trauma were generated and scored. Mechanical overload was applied by single uniaxial 50% compression followed by immediate release, and the explants were live-dead stained (n = 20 explants). Type VI collagen, the major PCM component, was fluorescent stained and the extent was determined, in which individual cells were enclosed by a recognizable PCM; this was termed PCM fraction. More than 50% of chondrocytes in all degenerative IVD explants displayed <25% PCM fraction and a lower PCM fraction correlated with higher cell numbers (p < 0.001), suggesting a PCM structural impairment in IVD degeneration that is associated with chondrocyte clustering. Mechanical overload-induced significantly increased cell death (p = 0.005), and the PCM fraction was significantly lower in overload-induced cell death than in live cells (p = 0.042), suggesting that a fully present PCM has a protective role in mechanical overload. Collectively, human IVD degeneration is associated with a structural impairment of the PCM, which may promote cell death under mechanical overload.
Using two-dimensional top-down view microscopy, researchers have recently described chondrocytes as being spatially arranged in distinct patterns such as strings, double strings, and small and large clusters. Because of the seeming association of these changes with tissue degeneration, they have been proposed as an image-based biomarker for early osteoarthritis (OA) staging. The aim of our study was to investigate the spatial arrangement of chondrocytes in human articular cartilage in a 3D fashion and to evaluate the 3D changes of these patterns in the context of local tissue destruction. Decalcified femoral condyle resections from the load-bearing area were analysed in 3D for their spatial chondrocyte organisation by means of fluorescence microscopy and synchrotron-radiation micro-computed tomography (SR-µCT). In intact cartilage chondrocyte strings can be found in the superficial, transitional and deep zones. The proposed pattern changes accompanying tissue destruction could be located not just along the surface but also through all layers of cartilage. Each spatial pattern was characterised by a different cellular density (the only exception being between single and double strings with p = 0.062), with cellular density significantly increasing alongside the increase in local tissue degeneration as defined by the chondrocyte patterns. We can thus corroborate that the proposed cellular spatial changes are a three-dimensional function of local tissue degeneration, underlining their relevance as an image-based biomarker for the early diagnosis and description of OA.Clinical trial registration number: Project number of the ethics committee of the University of Tübingen:171/2014BO2.
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