Identification of Distinct Metabolic Pools of Aggrecan and Their Relationship to Type VI Collagen in the Chondrons of Mature Bovine Articular Cartilage Explants

Gm, Winter; Ca, Poole; Mz, Ilic; Ross, Jacqueline M.; Hc, Robinson; Cj, Handley

doi:10.3109/03008209809002445

Cited by 17 publications

(10 citation statements)

References 14 publications

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“…3), were consistent with previous observations of bovine cartilage 14,20 and around human chondrocytes. 21 The pericellular matrix (within ,2 mm of the cell membrane) exhibited the most rapid rates of PG deposition, which decreased nearly monotonically with increasing distance from chondrocytes regardless of experimental conditions (Fig.…”

Section: Resultssupporting

confidence: 93%

Controlled Enzymatic Matrix Degradation for Integrative Cartilage Repair: Effects on Viable Cell Density and Proteoglycan Deposition

Quinn

Hunziker

2002

Tissue Engineering

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Controlled enzymatic degradation has previously been shown to promote integrative repair of cartilage defect surfaces. However, side effects of such treatments could include decreases in chondrocyte viability or matrix synthesis. To explore the importance of these potential side effects, partial-thickness defects were introduced bilaterally into cartilage of the distal femur of 25 adult rabbits, previously developed treatments involving application of either chondroitinase ABC (1 U/mL) or 2.5% trypsin in saline were applied unilaterally, and rabbits were then allowed to walk freely for 2 weeks to 6 months. Before euthanasia, [(35)S]sulfate was injected into joint cavities for radiolabeling of newly synthesized cartilage proteoglycans. Vertical sections of cartilage and bone were obtained from defect areas and prepared for histological autoradiography and morphometry. Chondrocyte and cartilage morphology and cell-associated matrix proteoglycan deposition were assessed as functions of distance from introduced defects. Consistent with previous studies, chondrocyte density appeared to decrease within a 100-microm-thick region next to defects ("near") compared with control cartilage farther from the defect. Enzyme treatments strengthened the difference in cell density between regions near the defect and control regions far from it. However, for regions near defects, no significant changes in cell density were measured as a result of enzyme treatments; results suggest that creation of the defect itself has the most important long-term negative impact on nearby cell density. Furthermore, no long-term effects on cell volumes or cell-associated proteoglycan deposition due to enzyme treatments could be detected. Use of these controlled enzyme treatments may therefore be a clinically safe measure for promotion of integrative repair of articular cartilage.

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Section: Resultssupporting

confidence: 93%

Controlled Enzymatic Matrix Degradation for Integrative Cartilage Repair: Effects on Viable Cell Density and Proteoglycan Deposition

Quinn

Hunziker

2002

Tissue Engineering

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“…These findings are consistent with studies using other joint connective tissues such as articular cartilage [15] and collateral ligament [10]. In the case of articular cartilage, it has been shown that the majority of newly synthesized aggrecan remains closely associated with the chondrocytes [16,17]. However, the majority of the chemical pool of aggrecan resides in the interterritorial matrix and it is this population that is responsible for the biomechanical properties of cartilage.…”

Section: Discussionsupporting

confidence: 89%

Large aggregating and small leucine‐rich proteoglycans are degraded by different pathways and at different rates in tendon

Samiric

Ilic

Handley

2004

European Journal of Biochemistry

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S]sulfate lost to the medium and retained in the matrix was determined for each day in culture. It was shown that the rate of catabolism of radiolabelled small proteoglycans (decorin and biglycan) was significantly slower (T ½ > 20 days) compared with the radiolabelled large proteoglycans (aggrecan and versican) that were rapidly lost from the tissue (T ½ 2 days). Both the small and large newly synthesized proteoglycans were lost from the matrix with either intact or proteolytically modified core proteins. When explant cultures of tendon were maintained either at 4°C or in the presence of the lysosomotrophic 2 agent ammonium chloride, inhibition of the cellular catabolic pathway for small proteoglycans was demonstrated indicating the involvement of cellular activity and lysosomes in the catabolism of small proteoglycans. It was estimated from these studies that approximately 60% of the radiolabelled small proteoglycans that were lost from the tissue were degraded by the intracellular pathway present in tendon cells. This work shows that the pathways of catabolism for large aggregating and small leucine-rich proteoglycans are different in tendon and this may reflect the roles that these two populations of proteoglycans play in the maintenance of the extracellular matrix of tendon.

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“…It forms a “cargo‐net like” organization around each chondrocyte in vitro (29) . In addition, type IX collagen, type II collagen, and aggrecan have been identified as components of pericellular matrix (30–32) . However, it is not known how these various molecules, which include both collagens and proteoglycans, form a pericellular matrix network.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, the role of pericellular matrix molecules was studied by correlating the presence of a particular matrix molecule to its function after enzymatic or mechanical isolation of chondrons (8,32) . Alteration of the content of pericellular matrix molecules such as type VI collagen was also achieved by treatment of chondrocytes with cytokines including IL‐1 (30) . However, such studies were correlative in nature, because the contents of multiple matrix molecules and matrix degradation enzymes may be altered simultaneously by such treatment.…”

Section: Discussionmentioning

confidence: 99%

Pericellular Matrilins Regulate Activation of Chondrocytes by Cyclic Load-Induced Matrix Deformation

Kanbe

Yang

Wei

et al. 2007

Journal of Bone and Mineral Research

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Pericellular matrix is at the ideal location to be involved in transmitting mechanical signals from the microenvironment to a cell. We found that changes of the content of matrilins that link various pericellular molecules surrounding chondrocytes affect mechanical stimulation of chondrocyte proliferation and gene expression. Thus, pericellular matrilins may play a role in chondrocyte mechanotransduction.Introduction: Chondrocytes reside in a capsule of pericellular matrix (chondron), which has been hypothesized to play a critical role in transducing mechanical signals to the cell. In this study, we test the hypothesis that the levels of matrilin (MATN)-1 and -3, major components of the chondrocyte pericellular matrix network, regulate activation of chondrocyte proliferation and differentiation by cyclic load-induced matrix deformation. Materials and Methods: Functional matrilins were decreased by expressing a dominant negative mini-MATN in primary chondrocytes or by using MATN1-null chondrocytes. The abundance of matrilins was also increased by expressing a wildtype MATN1 or MATN3 in chondrocytes. Chondrocytes were cultured in a 3D sponge subjected to cyclic deformation at 1 Hz. Chondrocyte gene expression was quantified by real-time RT-PCR and by Western blot analysis. Matrilin pericellular matrix assembly was examined by immunocytochemistry. Results: Elimination of functional matrilins from pericellular matrix abrogated mechanical activation of Indian hedgehog signaling and abolished mechanical stimulation of chondrocyte proliferation and differentiation. Excessive or reduced matrilin content decreased mechanical response of chondrocytes. Conclusions: Normal content of matrilins is essential to optimal activation of chondrocytes by mechanical signals. Our data suggest that the sensitivity of chondrocytes to the changes in the microenvironment can be adjusted by altering the content of matrilins in pericellular matrix. This finding supports a critical role of pericellular matrix in chondrocyte mechano-transduction and has important implications in cartilage tissue engineering and mechanical adaptation.

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Identification of Distinct Metabolic Pools of Aggrecan and Their Relationship to Type VI Collagen in the Chondrons of Mature Bovine Articular Cartilage Explants

Cited by 17 publications

References 14 publications

Controlled Enzymatic Matrix Degradation for Integrative Cartilage Repair: Effects on Viable Cell Density and Proteoglycan Deposition

Controlled Enzymatic Matrix Degradation for Integrative Cartilage Repair: Effects on Viable Cell Density and Proteoglycan Deposition

Large aggregating and small leucine‐rich proteoglycans are degraded by different pathways and at different rates in tendon

Pericellular Matrilins Regulate Activation of Chondrocytes by Cyclic Load-Induced Matrix Deformation

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