Evidence for enhanced collagen type III deposition focally in the territorial matrix of osteoarthritic hip articular cartilage

Abstract

SUMMARY Objective To determine if type III collagen is concentrated in the chymotrypsin-extractable collagen pool from osteoarthritic articular cartilage to assess its potential as a biomarker of Osteoarthritis (OA) pathogenic mechanisms. Methods Full thickness articular cartilage from grossly normal surfaces was analyzed from femoral heads, obtained at hip replacement surgery, from OA (n = 10) and fracture (n = 10) patients. Collagen, extracted by α-chymotrypsin, was characterized by SDS-PAGE/Western blot analysis, ELISA and immunohistochemistry using monoclonal antibodies specific to collagens types II and III. Results α-Chymotrypsin extracted more collagen from OA than control cartilage. The extractable pool included collagen types II and III from both OA and control hips. Importantly, OA cartilage contained 6-fold more collagen type III than control cartilage, based on ELISA. The estimated total tissue ratio of collagen III/II was in the 1–10% range for individual OA cartilage samples, based on pepsin-solubilized collagen using SDS-PAGE densitometry. Collagen type III N-propeptide trimers were the main molecular fragments seen on Western blot analysis of OA and control extracts. The chymotrypsin-extracted type II collagen gave primarily full-length α1(II) chains and chain fragments of α1(II) on Western blot analysis from both OA and control tissues. Immunohistochemistry showed that type III collagen was more concentrated in the upper half of OA cartilage and in the territorial matrix around individual chondrocytes and chondrocyte clusters. Conclusions The findings confirm that collagen type III deposition occurs in adult articular cartilage but significantly more pronounced in osteoarthritic joints, presenting a potential marker of matrix repair or pathobiology.

Unique charge-dependent constraint on collagen recognition by integrin α10β1

“…No other peptide (or shorter derivatives) from Toolkit III approached the binding activity of III-7/GLOGEN. In the setting of cartilage, collagen III, although enriched in the pericellular environment, is much less abundant than collagen II [22], and its expression increases with age or with the onset of osteoarthritis [23]. However, collagen II, the main fibrillar collagen of cartilage, lacks GLOGEN but contains GLOGER which binds α10β1 better than GFOGER, second only to GLOGEN, and GVOGEA which is shown here to be a moderately good ligand for α10β1.…”

“…The increased expression of collagen III has been proposed as a repair response after damage or disease in cartilage [23]. The inability of the major chondrocyte integrin, α10β1, to engage with the major integrin locus in collagen III, GROGER, suggests instead that this collagen should rather be regarded as a marker for cartilage dysfunction or resorption.…”

Selective Enzymatic Digestion of Proteoglycans and Collagens Alters Cartilage T1rho and T2 Relaxation Times

“…Interestingly, T2 relaxation times have been found to be higher in cartilage with moderate OA compared to severe OA [9, 19] possibly due to alterations in collagen alignment and organization near the articular surface that occur before the loss of extracellular matrix during OA progression [4, 17, 55] . In the present study, to measure degraded collagen we treated explants with α-chymotrypsin to solubilize the extractable (cleaved) collagen [3, 21, 22] . We have previously shown a significant increase in the percentage of extractable collagen in OA regions of cartilage compared to normal regions of cartilage within the same joint [19] .…”

Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis

“…In addition to type II collagen, several recent studies have investigated potential markers that come from type III and type X collagen [30,31]. OA is characterized by the changing of the chondrocyte phenotype into one of hypertrophy [2] and increased expression of collagen type X is a hallmark of this change.…”