The Pericellular Matrix as a Transducer of Biomechanical and Biochemical Signals in Articular Cartilage

Abstract

The pericellular matrix (PCM) is a narrow tissue region surrounding chondrocytes in articular cartilage, which together with the enclosed cell(s) has been termed the "chondron." While the function of this region is not fully understood, it is hypothesized to have important biological and biomechanical functions. In this article, we review a number of studies that have investigated the structure, composition, mechanical properties, and biomechanical role of the chondrocyte PCM. This region has been shown to be rich in proteoglycans (e.g., aggrecan, hyaluronan, and decorin), collagen (types II, VI, and IX), and fibronectin, but is defined primarily by the presence of type VI collagen as compared to the extracellular matrix (ECM). Direct measures of PCM properties via micropipette aspiration of isolated chondrons have shown that the PCM has distinct mechanical properties as compared to the cell or ECM. A number of theoretical and experimental studies suggest that the PCM plays an important role in regulating the microenvironment of the chondrocyte. Parametric studies of cell-matrix interactions suggest that the presence of the PCM significantly affects the micromechanical environment of the chondrocyte in a zone-dependent manner. These findings provide support for a potential biomechanical function of the chondrocyte PCM, and furthermore, suggest that changes in the PCM and ECM properties that occur with osteoarthritis may significantly alter the stress-strain and fluid environments of the chondrocytes. An improved understanding of the structure and function of the PCM may provide new insights into the mechanisms that regulate chondrocyte physiology in health and disease.

TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading

“…Moreover, whereas compressive loading of intact cartilage explants can stimulate proteoglycan synthesis immediately (1,27), the response of chondrocytes embedded in agarose is enhanced with additional weeks of preculture (28). Cell-matrix interactions in the pericellular region are believed to play a critical role in transducing mechanical signals (29)(30)(31). Several studies smaller than all other groups (P < 0.05); **less than control and GSK205, greater than Loaded+GSK205 (P < 0.05), n = 4-6, mean ± SEM.…”

“…Previous studies have observed [Ca 2+ ] i signaling in response to mechanical loading (38,39); interestingly, these studies detected [Ca 2+ ] i signaling in chondrocyte-laden constructs without substantial preculture (<72 h), although chondrocytes synthesize small amounts of pericellular proteoglycans even within 2 d of culture in agarose (29) that could contribute to mechanically induced [Ca 2+ ] i signaling. Thus, the effects of loading with and without preculture, observed in this study as well as in previous studies, may be due to differences in the characteristics of the [Ca 2+ ] i signal with preculture, or perhaps other environmental and cellular factors that change over time (24,26,28,40).…”

Mice Lacking the Extracellular Matrix Protein WARP Develop Normally but Have Compromised Peripheral Nerve Structure and Function

“…In mature articular cartilage, WARP has a highly restricted localization in the chondrocyte pericellular matrix, a structure with important roles in facilitating cellmatrix interactions and in maintaining cartilage homeostasis, particularly in detecting and responding to changes in mechanical stimuli (26,27). We predicted that ablating WARP expression would disrupt the pericellular matrix, which may alter interactions of chondrocytes with their surrounding matrix and, potentially, their response to mechanical forces.…”

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

“…The strings of mid and inner annular cells embedded in a dense pericellular matrix, located between adjacent lamellae, largely spared these tensile strains. However, the annular cells of the outer AF with their extensive interdigitating cellular processes woven into the collagenous architecture would be expected to be subjected to tensional forces in situ and may be involved in annular mechanotransduction events [38]. The morphologic complexity of the annular cells with their interwoven ECM attachments to the annular collagen fibres indicates that the load transfer from ECM to cell membrane to cytoskeleton in all likelihood occurs by a complex pathway.…”