Severe disturbance of the distribution and expression of type VI collagen chains in osteoarthritic articular cartilage

Abstract

Objective. The aim of this study was to evaluate the messenger RNA (mRNA) expression and distribution of the major pericellular type VI collagen in normal and osteoarthritic (OA) cartilage.Methods. Conventional and confocal laser scanning immunohistochemistry, as well as in situ hybridization experiments, were performed for all 3 collagen type VI chains in sections of normal and OA articular cartilage.Results. individual microfibrillar network in virtually all connective tissues (1-4). In hyaline articular cartilage, type V1 collagen has thus far been described in the immediate pericellular matrix (5-8), and is therefore an integral component of the chondron, the functional unit of the articular cartilage (9,lO). This local restriction is the main reason why type VI collagen represents only a small portion (<2%) of all cartilage collagens (11).The composition of the pericellular matrix of articular chondrocytes is different in many respects from that of the territorial and interterritorial cartilage matrix. Thus, besides type VI collagen, it contains increased amounts of specifically composed proteoglycans (1 2), other collagens such as types IX (13) and XI (14), and noncollagenous components (15). The function of type VI collagen in articular cartilage is still unclear, but it is likely to be different from that in other connective tissues, where it is not associated with cells. Type VI collagen has been shown to bind to integrins of the chondrocyte membrane, though the exact interaction remains unclear (16,17). Additionally, type VI collagen binds to other proteins of the pericellular matrix, such as other collagens, decorin, fibromodulin, hyaluronan, and fibronectin (18)(19)(20). Thus. type VI collagen might act as an interface between the rigid interterritorial cartilage matrix and the chondrocyte, and is presumably involved in cell anchoring as well as matrix-cell signaling (21).The hallmark of osteoarthritic (OA) cartilage degeneration is the destruction and, finally, the erosion of the extracellular cartilage matrix. This implies degradation, as well as increased synthesis, of cartilage matrix components. Most investigations so far have analyzed the biochemistry of the major components of the interterritorial cartilage matrix, and many data have accumulated about synthesis and degradation of, for example, type I1 collagen and aggrecan (22)(23)(24)(25). Much less attention has been given to the changes in the pericellular matrix and its turnover by the chondrocytes. Poole et a1

Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro

“…In contrast, MMP-1 was expressed only at very low levels in both normal (3) and OA articular chondrocytes in vivo. MMP-1 may be involved in the basic pericellular collagenous matrix turnover (36) that is found in both normal and OA cartilage (37). However, our data support previous indirect biochemical evidence (9) suggesting that MMP-1 is not primarily involved in interterritorial collagen breakdown in OA cartilage, although a role in disease stages that were not represented in our specimens cannot be excluded.…”

Activation of Interleukin-1 Signaling Cascades in Normal and Osteoarthritic Articular Cartilage

“…16,20 The few cells that did not stain positive for the investigated molecules, particularly in the osteoarthritic samples, might indicate individual damaged cells with aberrant gene expression pattern, which we have described for other genes as well. 24,28 Tissue culture studies confirmed that the ERK, JNK, p38, and NF-B pathways can be activated in articular chondrocytes as indicated by the presence of the phosphorylated isoforms or nuclear translocation of NF-B after IL-1␤ stimulation. These data confirm on the tissue level in vitro experiments using isolated chondrocytes as those performed in this and other studies.…”

“…24 Fluorochrome-labeled secondary antibodies (fluorescein isothiocyanate, Texas Red; and Cy-5, Dianova, Hamburg, Germany) were used for visualization of the antigens. Nuclear DNA was counterstained with propidium iodide.…”

Advanced Osteoarthritis in Humans Is Associated With Altered Collagen VI Expression and Upregulation of ER-stress Markers Grp78 and Bag-1

“…(J Histochem Cytochem 57:923-931, 2009) K E Y W O R D S osteoarthritis cartilage ER stress bag-1 grp78 collagen VI NG2 OSTEOARTHRITIS (OA) IS A PROGRESSIVE DISEASE, with changes in chondrocyte gene expression and extracellular matrix (ECM) composition occurring before macroscopic structural damage is observed (Hamerman 1989). Articular chondrocytes in OA exhibit a hypermetabolic phenotype, with studies describing highly proliferative clonal chondrocytes, along with the upand downregulation of ECM molecules such as aggrecan (Matyas et al 1995), collagen II (Matyas et al 1995), perlecan (Tesche and Miosge 2004), metalloproteases (Mitchell et al 1996;Reboul et al 1996;Billinghurst et al 1997), aggrecanases (Lark et al 1997;Naito et al 2007), fibronectin (Wurster and Lust 1984;Brown and Jones 1990), collagen I (Deshmukh and Root 1974), and collagen VI (Hambach et al 1998;Pullig et al 1999). Etiologies ranging from genetic inheritance to trauma and aging can all contribute to the onset of OA, and further changes in gene expression occur as the disease progresses (Hardingham 2008).…”