Elsevier

Acta Biomaterialia

Volume 1, Issue 3, May 2005, Pages 317-325
Acta Biomaterialia

The biomechanical role of the chondrocyte pericellular matrix in articular cartilage

https://doi.org/10.1016/j.actbio.2005.02.001Get rights and content

Abstract

The pericellular matrix (PCM) is a narrow tissue region that surrounds chondrocytes in articular cartilage. Previous parametric studies of cell–matrix interactions suggest that the mechanical properties of the PCM relative to those of the extracellular matrix (ECM) can significantly affect the micromechanical environment of the chondrocyte. The goal of this study was to use recently quantified mechanical properties of the PCM in a biphasic finite element model of the cell–PCM–ECM structure to determine the potential influence of the PCM on the mechanical environment of the chondrocyte under normal and osteoarthritic conditions. Our findings suggest that the mismatch between the Young’s moduli of PCM and ECM amplifies chondrocyte compressive strains and exhibits a significant stress shielding effect in a zone-dependent manner. Furthermore, the lower permeability of PCM relative to the ECM inhibits fluid flux near the cell by a factor of 30, and thus may have a significant effect on convective transport to and from the chondrocyte. Osteoarthritic changes in the PCM and ECM properties significantly altered the mechanical environment of the chondrocyte, leading to ∼66% higher compressive strains and higher fluid flux near the cell. These findings provide further support for a potential biomechanical role for the chondrocyte PCM, and suggest that changes in the properties of the PCM with osteoarthritis may alter the stress–strain and fluid flow environment of the chondrocytes.

Introduction

Articular cartilage is an avascular, aneural connective tissue that lines the surfaces of diarthrodial joints and serves as the low-friction, load-bearing material for joint motion. A single type of cell––the chondrocyte––maintains the extracellular matrix (ECM) of this tissue through a balance of anabolic and catabolic activities. During normal joint activity, chondrocytes are exposed to a complex mechanical environment that is characterized by time- and spatially-varying stresses and strains, hydrostatic pressure, interstitial fluid flow, streaming potentials and osmotic pressure changes [1], [2], [3], [4], [5]. This micromechanical environment of chondrocytes, in conjunction with biochemical factors (e.g., growth factors, cytokines), plays an important role in cartilage homeostasis and, as a consequence, the health of the joint [6], [7], [8], [9], [10].

Chondrocytes in articular cartilage are surrounded by a narrow tissue region termed the pericellular matrix (PCM). The PCM is primarily characterized by the presence of type VI collagen but also possesses a high concentration of proteoglycans, including aggrecan, hyaluronan, and decorin, as well as fibronectin, and types II and IX collagen [11]. The PCM and the chondrocyte together have been termed the “chondron” [11], [12]. This region was first described by Benninghoff [13] as a “fluid filled bladder”, but was not investigated until the presence of intact chondrons was observed as a byproduct of cartilage homogenization [14]. Chondrons can be isolated either mechanically or enzymatically and previous studies have performed detailed characterizations of their structure, composition, metabolic activity, and mechanical properties [12], [15], [16], [17], [18], [19], [20], [21].

Although the precise function of the PCM is still unknown, there has been considerable speculation that it plays a biomechanical role in cartilage [12], [14], [21], [22], [23], [24], [25]. For example, it has been hypothesized that the PCM may provide a protective effect for the chondrocytes during loading through an “adaptive water loss from PCM proteoglycans” [25]. Other studies have suggested that the chondron serves as a mechanical transducer [12], [14], [22], [23], potentially through an interaction of type VI collagen with cell surface integrins or hyaluronan [26], [27], [28]. Recent studies also show that deletion of col6a1 gene in mice results in a significant loss of PCM modulus, and is associated with accelerated osteoarthritic changes in the hip joint [17], providing indirect evidence for the role of the PCM. These hypotheses are supported by previous theoretical models of cell–matrix interactions in cartilage, which suggest that the ratio of mechanical properties of the PCM and the ECM may significantly influence the mechanical environment of the chondrocyte [24], [29]. In these studies, however, the biphasic properties of the chondron were not known and were examined parametrically over a range of values.

Several studies have used either theoretical or experimental models to characterize the micromechanical environment of the chondrocytes to better understand the sequence of events through which these signals are converted to an intracellular response [3], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38]. The predictions of these models rely on physiologically relevant measures of the material properties of the components ECM, PCM, and chondrocyte. The mechanical properties of the cartilage ECM have been well-characterized in tension, compression, and shear with substantial evidence of both flow-dependent and flow independent viscoelastic behaviors [39], [40], [41], [42], [43] that have been shown to vary significantly with depth from the tissue surface [33], [44], [45], [46]. The elastic and viscoelastic properties of chondrocytes have also been determined using gel compression [47], [48], micropipette aspiration [49], [50], [51], [52], and cytoindentation [53]. More recently, the mechanical properties of normal and osteoarthritic chondrons was measured using the micropipette technique coupled with theoretical formulations of an elastic half space model [16] or a biphasic finite element model [15]. From these studies, the Young’s modulus, hydraulic permeability, and Poisson’s ratio of the PCM from normal and osteoarthritic human articular cartilage were determined.

The goal of this study was to combine direct measurements of PCM properties with an axisymmetric linear biphasic finite element model to examine the biomechanical role of the PCM on the stress–strain and fluid flow environments of the chondrocyte. We tested the hypothesis that the decreased Young’s modulus and the low permeability of the PCM compared to that of ECM lead to altered stresses, strains, and fluid fluxes around the chondrocyte in a zone-dependent manner. A second goal was to determine if changes in the biomechanical properties of the ECM and PCM due to osteoarthritis affect the micromechanical environment of the cell.

Section snippets

Materials and methods

A custom-written axisymmetric, linear, biphasic finite element model was used to analyze the mechanical role of the PCM. This finite element model uses the Galerkin weighted residual method applied to a up formulation of the biphasic theory and treats solid displacement, u, and pressure, p, as essential variables computed at element nodes [54]. In this formulation, the balance of linear momentum for the mixture is given by:·σe-p=0where σe is the elastic, or effective Cauchy stress tensor and

Results

The thickness of the PCM had little effect on the local strain environment of the cell, especially in the surface and in the middle zones (Fig. 3). A 50% increase in the osteoarthritic PCM thickness lead to a maximum of 12% increase of the cell strain in the superficial zone (i.e., zone 1) and less than 2% increase in cell strain in the deep zone (i.e., zone 6). In addition, the PCM thickness had little effect on the local fluid flux around the cell. For example, a hypothetical increase in the

Discussion

The findings of our theoretical model provide evidence that the presence of the PCM has a dramatic influence on the local stress–strain and fluid flow environment of the chondrocyte. The lower permeability of the PCM relative to that of the ECM inhibits fluid flow inside the chondron by a factor of thirty. In addition, the lower PCM stiffness compared to the ECM amplifies the tissue strain by a factor of 2–3, depending on the zone of the cartilage (Fig. 5, Fig. 8). The highest amplification

Acknowledgement

The authors would like to thank Maureen Upton for important discussions during the early segments of this study. This study was supported by the National Institutes of Health grants AR48182, AG15768, AR50245, AR47442, AR45644 and by a graduate fellowship to LGA from the Center for Biomolecular and Tissue Engineering (GM08555).

References (77)

  • C.C. Wang et al.

    Optical determination of anisotropic material properties of bovine articular cartilage in compression

    J Biomech

    (2003)
  • A. Mobasheri et al.

    Integrins and stretch activated ion channels; putative components of functional cell surface mechanoreceptors in articular chondrocytes

    Cell Biol Int

    (2002)
  • G.A. Ateshian et al.

    Finite deformation biphasic material properties of bovine articular cartilage from confined compression experiments

    J Biomech

    (1997)
  • R.Y. Hori et al.

    Indentation tests of human articular cartilage

    J Biomech

    (1976)
  • S.S. Chen et al.

    Depth-dependent compressive properties of normal aged human femoral head articular cartilage: relationship to fixed charge density

    Osteoarthr Cartilage

    (2001)
  • M.M. Knight et al.

    Cell and nucleus deformation in compressed chondrocyte-alginate constructs: temporal changes and calculation of cell modulus

    Biochim Biophys Acta

    (2002)
  • W.R. Jones et al.

    Alterations in the Young’s modulus and volumetric properties of chondrocytes isolated from normal and osteoarthritic human cartilage

    J Biomech

    (1999)
  • G.M. Lee et al.

    The incidence of enlarged chondrons in normal and osteoarthritic human cartilage and their relative matrix density

    Osteoarthr Cartilage

    (2000)
  • S. Park et al.

    Microscale frictional response of bovine articular cartilage from atomic force microscopy

    J Biomech

    (2004)
  • C.T. Hung et al.

    What is the role of the convective current density in the real-time calcium response of cultured bone cells to fluid flow?

    J Biomech

    (1996)
  • W.R. Trickey et al.

    The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes

    J Orthop Res

    (2004)
  • G.A. Ateshian et al.

    The correspondence between equilibrium biphasic and triphasic material properties in mixture models of articular cartilage

    J Biomech

    (2004)
  • E.H. Frank et al.

    Cartilage electromechanics—I. Electrokinetic transduction and the effects of electrolyte pH and ionic strength

    J Biomech

    (1987)
  • W.Y. Gu et al.

    Transport of fluid and ions through a porous-permeable charged-hydrated tissue, and streaming potential data on normal bovine articular cartilage

    J Biomech

    (1993)
  • G.R. Erickson et al.

    Hyper-osmotic stress induces volume change and calcium transients in chondrocytes by transmembrane, phospholipid, and G-protein pathways

    J Biomech

    (2001)
  • F. Guilak et al.

    The effects of osmotic stress on the viscoelastic and physical properties of articular chondrocytes

    Biophys J

    (2002)
  • J.P. Urban et al.

    Regulation of proteoglycan synthesis rate in cartilage in vitro: influence of extracellular ionic composition

    Biochim Biophys Acta

    (1989)
  • W.A. Hing et al.

    The influence of the pericellular microenvironment on the chondrocyte response to osmotic challenge

    Osteoarthr Cartilage

    (2002)
  • L. You et al.

    A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix

    J Biomech

    (2001)
  • W.M. Lai et al.

    A triphasic theory for the swelling and deformation behaviors of articular cartilage

    J Biomech Eng

    (1991)
  • V.C. Mow et al.

    Mechano-electrochemical properties of articular cartilage: their inhomogeneities and anisotropies

    Ann Rev Biomed Eng

    (2002)
  • F. Guilak et al.

    Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis

    J Orthop Res

    (1994)
  • L.A. Setton et al.

    Mechanical properties of canine articular cartilage are significantly altered following transection of the anterior cruciate ligament

    J Orthop Res

    (1994)
  • R.A. Stockwell

    Structure and function of the chondrocyte under mechanical stress

  • G.P.J. van Campen et al.

    Cartilage and chondrocytes responses to mechanical loading in vitro

  • F. Guilak et al.

    Physical regulation of cartilage metabolism

  • C.A. Poole

    Articular cartilage chondrons: form function and failure

    J. Anat.

    (1997)
  • C.A. Poole

    Chondrons: the chondrocyte and its pericellular microenvironment

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      Chondrocytes are surrounded by a thin (2–4 µm thick) collagen type VI rich tissue region known as the pericellular matrix (PCM) [4,5]. The PCM regulates mechanical and biochemical signals to the chondrocytes [6–9], influencing cell metabolism, cartilage homeostasis, and overall joint health [10,11]. Alterations in PCM composition can change these signals and influence the biological responses of cells and, thus, cartilage mechanobiology and disease progression [7,8,12].

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