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.

Keywords: Aggrecan; Chondron; Decorin; Mechanobiology; Mechanotransduction; Osteoarthritis; Perlecan; Territorial matrix; Type II collagen; Type VI collagen.

Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1. Structure and morphology of the PCM

(A) Transmission electron microscopy (TEM) showing the chondrocyte within the pericellular, territorial, and extracellular matrices (scale bar = 1 μm). (B) Helium ion microscopy of a cell void within a cross-section of articular cartilage showing the basket-like morphology of the collagen in the pericellular matrix [adapted from (Vanden Berg-Foels et al., 2012), with permission]. (C) Immunohistochemistry for type VI collagen in the full thickness of articular cartilage. (D) Three-dimensional reconstruction of articular cartilage chondrons defined by type VI collagen [adapted from (Choi et al., 2007), with permission].

Figure 2. Methods of mechanical testing for determining the micromechanical properties of the PCM

(A) Isolated chondrons tested using micropipette aspiration [from (Alexopoulos et al., 2003), with permission]. (B) Immunofluorescence-guided atomic force microscopy of cartilage sections labeled for PCM molecules [adapted from (Wilusz and Guilak, 2014)]. (C) 3D reconstruction of compressed chondrons and computational modeling of chondron deformation [adapted from (Choi et al., 2007; Kim et al., 2010), with permission].

Figure 3. Stiffness mapping of the PCM in the superficial, middle, and deep zones of articular cartilage

(A-C) Representative immunofluorescence images showing the distribution of type VI collagen around cell-sized voids in superficial, middle, and deep zones. (D-F) Representative contour maps of calculated elastic moduli of the PCM in each zone. The spatial distribution of type VI collagen correlates well with lower modulus regions within each scan. Scale bar = 5 μm. [From (Wilusz et al., 2012b), with permission].

Figure 4. Alterations in the mechanical properties of the PCM with OA

(A, B) Representative contour maps of calculated elastic moduli of the PCM of normal (A) or osteoarthritic (B) cartilage. (C) Mean elastic modulus values with distance from the PCM inner edge of with and without OA. (D) Mean elastic moduli of the ECM and PCM, with and without OA, showing a loss of mechanical properties with OA. [Adapted from (Wilusz et al., 2013), with permission].

Figure 5. The pericellular matrix in other cartilaginous tissues

(A) (i) The intervertebral disc is composed of the annulus fibrosis (AF) and nucleus pulposus (NP); (ii) immunofluorescence for type VI collagen in the disc; (iii-v) collagen type VI surrounding cells in the NP, inner AF, and outer AF (scale bar = 20 μm). [Adapted from (Cao et al., 2007), with permission]. (B) (i) Knee meniscus histology and immunohistochemistry showing the variation in ECM and PCM labeling with meniscus region (scale = 0.2 mm, cell view: 20×20 μm); (ii) representative images of perlecan immunolabeling and elastic modulus maps in the outer, middle and inner regions of the knee meniscus [adapted from (Sanchez-Adams et al., 2013), with permission].