The structure and function of the pericellular matrix of articular cartilage

Abstract

Chondrocytes in articular cartilage are surrounded by a narrow pericellular matrix (PCM) that is both biochemically and biomechanically distinct from the extracellular matrix (ECM) of the tissue. While the PCM was first observed nearly a century ago, its role is still under investigation. In support of early hypotheses regarding its function, increasing evidence indicates that the PCM serves as a transducer of biochemical and biomechanical signals to the chondrocyte. Work over the past two decades has established that the PCM in adult tissue is defined biochemically by several molecular components, including type VI collagen and perlecan. On the other hand, the biomechanical properties of this structure have only recently been measured. Techniques such as micropipette aspiration, in situ imaging, computational modeling, and atomic force microscopy have determined that the PCM exhibits distinct mechanical properties as compared to the ECM, and that these properties are influenced by specific PCM components as well as disease state. Importantly, the unique relationships among the mechanical properties of the chondrocyte, PCM, and ECM in different zones of cartilage suggest that this region significantly influences the stress-strain environment of the chondrocyte. In this review, we discuss recent advances in the measurement of PCM mechanical properties and structure that further increase our understanding of PCM function. Taken together, these studies suggest that the PCM plays a critical role in controlling the mechanical environment and mechanobiology of cells in cartilage and other cartilaginous tissues, such as the meniscus or intervertebral disc.

Mechanical confinement regulates cartilage matrix formation by chondrocytes

“…The elastic moduli of the hydrogels used in these studies ranges from 2 kPa to 100 kPa 12,14,20,21 , which is comparable to the moduli of chondrocyte PCM, ranging from 10 kPa to 75 kPa 29 . Enhanced stiffness in covalently crosslinked PEG based hydrogels, found to exhibit minimal stress relaxation here, restricted production of sGAG and collagens, distribution of cartilage matrix, and proliferation of chondrocytes 20,21 .…”

“…2a). In addition, in the fast relaxing gels, chondrocytes formed canonical pericellular matrices (PCM), as indicated by staining for type VI collagen, and exhibited bean-shaped morphologies resembling those of chondrocytes in PCM in normal hyaline cartilage 29 (Fig. 2b, Supplementary Fig.…”

Mechanisms of osteocyte stimulation in osteoporosis

“…As there is no experimental data on the material properties of the PCM surrounding the osteocyte at present the properties of chondrocyte PCM, were assumed with an elastic modulus of 40 kPa and Poisson's ratio of 0.4 (Alexopoulos et al 2003;Alexopoulos et al 2005). While the PCM of chondrocytes differs from that of osteocytes in that it contains collagen, proteoglycans are the primary feature of both (Sauren et al 1992;Wilusz et al 2014;You et al 2004). Therefore we have assumed these values for the osteocyte PCM.…”

Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow

“…The relative material properties of chondrocytes, their pericellular environment and the extracellular matrix are also important to resolve the mechanical load sharing problem. The pericellular matrix has a significant role in the regulation of chondrocytes' mechanical environment and their mechanobiological response [41]. The region is primarily of type VI collagen, which is exclusive to this zone [41].…”