Osteoarthritis in the Human Knee: A Dynamic Process of Cartilage Matrix Degradation, Synthesis and Reorganization

Ar, Poole; Rizkalla, Geihan; Ionescu, Mirela; Reiner, A; Brooks, Elisabeth; Rorabeck, Cecil H.; Bourne, Roger; Bogoch, Earl R.

doi:10.1007/978-3-0348-7442-7_1

Cited by 56 publications

(59 citation statements)

References 25 publications

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“…Because these features are also seen in hypertrophic fetal growth plate chondrocytes, they may indicate a switch to some embryogenetic differentiation patterns in OA cartilage. In that, our findings would coincide with those made for other proteins of the growth plates: the expression of the growth plate-specific collagen Type X (Aigner et al 1993;Walker et al 1995), the shift in the proportions of large vs small proteoglycans (Poole et al 1993;Cs-Szabo et al 1995), the activation of metalloproteinases Cole et al 1996), and finally even the complex processes of pathological mineralization and of osteophyte formation in OA cartilage.…”

Section: Discussionsupporting

confidence: 87%

Expression of Anchorin CII (Cartilage Annexin V) in Human Young, Normal Adult, and Osteoarthritic Cartilage

Mollenhauer

Mok

King

et al. 1999

J Histochem Cytochem.

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SUMMARYIn its tissue-specific function as a collagen receptor of chondrocytes, cartilage annexin V (anchorin CII) occupies a key position in the organization of the cell-extracellular matrix (ECM) junction for the tissue. The general role of annexin V (Anx V) in other tissues suggests involvement in cellular secretory processes and in regulation of apoptosis. Immunohistochemical analysis of Anx V in growth plate cartilage, confirmed by in situ hybridization, suggests that Anx V is prominently expressed and forms a major constituent of growth plate chondrocytes. Anx V epitopes are also located in the pericellular matrix of hypertrophic cartilage. In adult articular cartilage the expression is downregulated, with the highest levels of immunostaining found in the upper third of the articular cartilage layers and almost no antigen found in the deep layers. Osteoarthritic (OA) cartilage is characterized by a significant upregulation of message and protein throughout the entire depth of the tissue, an accumulation of cytoplasmic annexin V epitopes, and a release of epitopes into the pericellular and interterritorial matrix, in part co-localized with granular structures. Therefore, Anx V expression and tissue distribution may serve as a histological marker for metabolic alterations and for changes in the cellular phenotype associated with OA.

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Section: Discussionsupporting

confidence: 87%

Expression of Anchorin CII (Cartilage Annexin V) in Human Young, Normal Adult, and Osteoarthritic Cartilage

Mollenhauer

Mok

King

et al. 1999

J Histochem Cytochem.

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“…Indeed this was supported by increased matrix deposition in hydrogels seeded with micro-aggregates. Likewise, the increase in biosynthesis in early cartilage lesions has been previously reported (Poole et al, 1993;Aurich et al, 2005). Comparable shifts from catabolic to the anabolic responses have been recently reported to occur by varying the exposure of chondrocytes to different oxygen percentages (Strobel et al, 2010).…”

Section: Discussionsupporting

confidence: 67%

High throughput generated micro-aggregates of chondrocytes stimulate cartilage formation in vitro and in vivo

Teixeira

Leijten²,

Sobral³

et al. 2012

eCM

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Cell-based cartilage repair strategies such as matrixinduced autologous chondrocyte implantation (MACI) could be improved by enhancing cell performance. We hypothesised that micro-aggregates of chondrocytes generated in high-throughput prior to implantation in a defect could stimulate cartilaginous matrix deposition and remodelling. To address this issue, we designed a micromould to enable controlled high-throughput formation of micro-aggregates. Morphology, stability, gene expression profiles and chondrogenic potential of micro-aggregates of human and bovine chondrocytes were evaluated and compared to single-cells cultured in micro-wells and in 3D after encapsulation in Dextran-Tyramine (Dex-TA) hydrogels in vitro and in vivo. We successfully formed micro-aggregates of human and bovine chondrocytes with highly controlled size, stability and viability within 24 hours. Micro-aggregates of 100 cells presented a superior balance in Collagen type I and Collagen type II gene expression over single cells and micro-aggregates of 50 and 200 cells. Matrix metalloproteinases 1, 9 and 13 mRNA levels were decreased in micro-aggregates compared to singlecells. Histological and biochemical analysis demonstrated enhanced matrix deposition in constructs seeded with micro-aggregates cultured in vitro and in vivo, compared to single-cell seeded constructs. Whole genome microarray analysis and single gene expression profiles using human chondrocytes confirmed increased expression of cartilagerelated genes when chondrocytes were cultured in microaggregates. In conclusion, we succeeded in controlled highthroughput formation of micro-aggregates of chondrocytes. Compared to single cell-seeded constructs, seeding of constructs with micro-aggregates greatly improved neocartilage formation. Therefore, micro-aggregation prior to chondrocyte implantation in current MACI procedures, may effectively accelerate hyaline cartilage formation.

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“…Increased collagen synthesis specifically in the deeper OA cartilage is a central hallmark of osteoarthritis. 5,7,11,52 Collagen synthesis is a multiple step process consisting of collagen gene expression, translation, posttranslational modification, triple-helix formation, secretion, and cleavage of N-and C-propeptides in the extracellular space. Collagen prolyl-4-hydroxylase types I and II, which are highly expressed in chondrocytes, play a major role in the synthesis of type II collagen because of their ability to hydroxylate proline residues indispensable for collagen triple helix formation and efficient procollagen secretion.…”

Section: Discussionmentioning

confidence: 99%

“…During the course of osteoarthritis, increased degradation processes of the ECM by mechanical factors as well as activity of metalloproteinases and aggrecanases have been observed. 5,6 Ultimately, destruction of large parts of the collagen network and ion-binding capacity via loss of negatively charged proteoglycans lead to a significantly decreased water-binding capability of the ECM. These biochemical changes are responsible for the devel-opment of the biophysical hallmarks of OA cartilage: loss of shock-absorbing properties and soft structure.…”

mentioning

confidence: 99%

Regulation of Type II Collagen Synthesis during Osteoarthritis by Prolyl-4-Hydroxylases

Grimmer

Balbus

Lang

et al. 2006

The American Journal of Pathology

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Osteoarthritic (OA) chondrocytes are metabolically active, displaying increased synthesis of type II collagen. Here, we show by immunohistochemistry and polymerase chain reaction that in comparison with healthy cartilage, OA articular chondrocytes exhibit increased in vivo synthesis of collagen prolyl-4-hydroxylase type II, a pivotal enzyme in collagen triple helix formation. Exposure of primary human articular chondrocytes to 1% oxygen enhanced accumulation of native type II collagen and stabilized hypoxia-inducible factor-1␣ (HIF-1␣). This effect was abolished by addition of the HIF-1 inhibitor 2-methoxyestradiol. Real-time polymerase chain reaction analyses of mRNAs from these cultures revealed increased transcript levels of both ␣-subunits of prolyl-4-hydroxylase (P4HA1, ϳ2-fold; P4HA2, ϳ2.3-fold) and of classical HIF-1 target genes (glucosetransporter-1, ϳ2.1-fold; phosphoglyceratekinase-1, ϳ2.2-fold). Treatment of hypoxic chondrocytes with 2-methoxyestradiol reduced transcriptional activity of HIF-1 and synthesis of ␣(II), and to a lesser extent ␣(I), subunits of collagen prolyl-4-hydroxylases. mRNA levels of type II collagen (Col2A1) and the ␤-subunit (P4HB) of prolyl-4-hydroxylase, however, displayed only modest changes at 1% oxygen. From these results and our in vivo data, we inferred that besides increased Articular hyaline cartilage is the most important component in synovial joints for frictionless joint motion. During movement, the articular cartilage is compressed by load and is then able to recover from this deformity. These unique biomechanical properties depend on the specific zonal architecture of articular cartilage as well as the extracellular matrix (ECM), which consists of two phases: solid and fluid phases. The main ECM components are proteoglycans, glycoproteins, and collagens, mainly type II collagen.1-3 Type II collagen is synthesized as a procollagen molecule with noncollagenous amino and carboxy extension peptides, by articular chondrocytes which represent the only living elements within hyaline cartilage. 4 Large type II collagen fibrils form a network with embedded proteoglycans, glycoproteins, water, and soluble ions. Since this collagen network is established in adults, the half-life of collagens is estimated to be over decades.Proper function of a load-bearing joint depends on the structural integrity of this highly specialized cartilage tissue and its ability to absorb and respond to mechanical stress. During the course of osteoarthritis, increased degradation processes of the ECM by mechanical factors as well as activity of metalloproteinases and aggrecanases have been observed. 5,6 Ultimately, destruction of large parts of the collagen network and ion-binding capacity via loss of negatively charged proteoglycans lead to a significantly decreased water-binding capability of the ECM. These biochemical changes are responsible for the devel-

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Osteoarthritis in the Human Knee: A Dynamic Process of Cartilage Matrix Degradation, Synthesis and Reorganization

Cited by 56 publications

References 25 publications

Expression of Anchorin CII (Cartilage Annexin V) in Human Young, Normal Adult, and Osteoarthritic Cartilage

Expression of Anchorin CII (Cartilage Annexin V) in Human Young, Normal Adult, and Osteoarthritic Cartilage

High throughput generated micro-aggregates of chondrocytes stimulate cartilage formation in vitro and in vivo

Regulation of Type II Collagen Synthesis during Osteoarthritis by Prolyl-4-Hydroxylases

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