Composition of Proteoglycans Synthesized in Different Layers of Cultured Anatomically Intact Articular Cartilage

Korver, G. H. V.; Stadt, R J van de; Kampen, G. P. J. Van; Korst, J. K. van der

doi:10.1016/s0934-8832(11)80147-2

Cited by 62 publications

(64 citation statements)

References 25 publications

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“…Metabolic differences between the two cell populations have been reported. SC synthesize less aggrecan [2] and collagen [3] than DC; they appear, however, to produce nonaggregating small proteoglycans in greater quantities [10]. The superficial cells secrete greater amounts of matrixdegrading metalloproteinases when stimulated with cytokines [5].…”

Section: Discussionmentioning

confidence: 99%

Isolation and differential secretion of metalloproteinase by superficial chondrocytes in articular cartilage

Takagi

Takahashi

Koshino

et al. 1998

International Orthopaedics

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Section: Discussionmentioning

confidence: 99%

Isolation and differential secretion of metalloproteinase by superficial chondrocytes in articular cartilage

Takagi

Takahashi

Koshino

et al. 1998

International Orthopaedics

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“…In general, increased sulfate incorporation, an indicator of proteoglycan synthesis, is detected in cartilage explants that have been cyclically loaded (4,5), whereas decreased synthesis occurs following static loading (5)(6)(7). The latter effect may be due to a reduction in fluid flow, with resultant decreases in oxygen uptake and ATP production (8).…”

Section: S-met/cys Into Proteins Secreted By Cartilage Explants or Bymentioning

confidence: 99%

Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded

Vincent¹,

Hermansson²,

Hansen³

et al. 2004

Arthritis & Rheumatism

119

106

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Objective. To determine whether the basic fibroblast growth factor (bFGF) mediates signal transduction in articular cartilage in response to mechanical loading.Methods. Articular cartilage from porcine metacarpophalangeal or knee joints was cyclically loaded (62.5-250N) for 2 minutes in the absence or presence of a bFGF receptor inhibitor, SB 402451 (250 nM). Activation of the extracellularly regulated kinase MAP kinase ERK was measured by Western blot analysis. Changes in protein synthesis were assessed by measuring the incorporation of 35 S-Met/Cys into proteins secreted by cartilage explants or by isolated chondrocytes.Results. Rapid activation of the ERK MAP kinase occurred when articular cartilage was loaded. This was dependent upon release of the bFGF because it was restricted by the FGF receptor inhibitor. Loaded explants were shown to release bFGF. Loading or bFGF stimulation of explants induced synthesis and secretion of tissue inhibitor of metalloproteinases 1 (TIMP-1), which was inhibited by SB 402451.Conclusion. Cyclical loading of articular cartilage causes bFGF-dependent activation of ERK and synthesis of TIMP-1.

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“…Cartilage is composed of a single cell lineage but differences in the organization, phenotype and function of cells in the various layers of cartilage have been recognized (1)(2)(3)(4). The superficial zone (SZ) is the most unique.…”

mentioning

confidence: 99%

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

Taniguchi

Caramés

Kawakami

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The superficial zone (SZ) of articular cartilage is critical in maintaining tissue function and homeostasis and represents the site of the earliest changes in osteoarthritis. Mechanisms that regulate the unique phenotype of SZ chondrocytes and maintain SZ integrity are unknown. We recently demonstrated that expression of the chromatin protein high mobility group box (HMGB) protein 2 is restricted to the SZ in articular cartilage suggesting a transcriptional regulation involving HMGB2 in SZ. Here, we show that an interaction between HMGB2 and the Wnt/␤-catenin pathway regulates the maintenance of the SZ. We found that the Wnt/␤-catenin pathway is active specifically in the SZ in normal mouse knee joints and colocalizes with HMGB2. Both Wnt signaling and HMGB2 expression decrease with aging in mouse joints. Our molecular studies show that HMGB2 enhances the binding of Lef-1 to its target sequence and potentiates transcriptional activation of the Lef-1-␤-catenin complex. The HMG domain within HMGB2 is crucial for interaction with Lef-1, suggesting that both HMGB2 and HMGB1 may be involved in this function. Furthermore, conditional deletion of ␤-catenin in cultured mouse chondrocytes induced apoptosis. These findings define a pathway where protein interactions of HMGB2 and Lef-1 enhance Wnt signaling and promote SZ chondrocyte survival. Loss of the HMGB2-Wnt signaling interaction is a new mechanism in aging-related cartilage pathology.aging ͉ osteoarthritis ͉ apoptosis ͉ superficial zone A rticular cartilage is a tissue that provides biomechanical properties that allow near frictionless joint movement and dispersion of mechanical loads. Cartilage is composed of a single cell lineage but differences in the organization, phenotype and function of cells in the various layers of cartilage have been recognized (1-4). The superficial zone (SZ) is the most unique. SZ cells produce lubricin, also termed proteoglycan-4 (PRG4) or superficial zone protein (SZP), an important joint lubricant (5-7), and are more responsive to stimulation by catabolic cytokines such as IL-1 (8). Recent studies also suggest that the SZ contains cells that express mesenchymal stem cell markers (9-11).Articular cartilage is among the tissues that undergo profound aging-related changes and aging represents the major risk factor for osteoarthritis (OA), the most prevalent joint disease (12). Agingrelated changes in cartilage include reduced cellularity, increased apoptosis and altered cellular responses to growth factors, cytokines and mechanical stress (13-15). Cartilage changes in aging and OA begin in the SZ and once the SZ is disrupted this is followed by progressive erosion of the remaining cartilage layers (16).To address mechanisms that maintain the unique phenotype of SZ cells we performed gene expression analyses and observed that expression of the chromatin protein HMGB2 is restricted to the SZ (17). Joint aging in humans and mice leads to loss of HMGB2 expression and this is correlated with the onset of OA-like changes. Mice deficient in Hm...

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Composition of Proteoglycans Synthesized in Different Layers of Cultured Anatomically Intact Articular Cartilage

Cited by 62 publications

References 25 publications

Isolation and differential secretion of metalloproteinase by superficial chondrocytes in articular cartilage

Isolation and differential secretion of metalloproteinase by superficial chondrocytes in articular cartilage

Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

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