Extracellular Distribution of Collagen II and Perifibrillar Adapter Proteins in Healthy and Osteoarthritic Human Knee Joint Cartilage

Abstract

Perifibrillar adapter proteins, interconnecting collagen fibrils, and linking the collagen network with the aggrecan matrix seem to play a crucial role in the pathogenesis of osteoarthritis (OA). Therefore, we examined immunohistochemically the extracellular distribution of collagen II and the main perifibrillar adapter proteins-collagen IX, decorin, cartilage oligomeric matrix protein (COMP), and matrilin-3-in human samples of healthy (n=4) and OA (n=42) knee joint cartilage. Histopathology assessment was performed using an OA score. Staining patterns were evaluated in relation to the disease stage. The perifibrillar adapter proteins were uniformly distributed in the upper zones of healthy cartilage. In moderate OA (n=8; score 14.3 ± 4.7), all proteins analyzed were locally absent in the fibrillated area or the superficial and upper mid zone. In advanced OA (n=20; score 18.9 ± 5.3), they were uniformly distributed in these zones and accumulated pericellularly. Perifibrillar adapter proteins are important for the stabilization of the collagen network in the upper zones of healthy cartilage. Their degradation might be a critical event in early OA. In advanced OA, there are indications for an increased synthesis in an attempt to regenerate the lost tissue and to protect the remaining cartilage from further destruction.

Serum Cartilage Oligomeric Matrix Protein in Late-Stage Osteoarthritis: Association with Clinical Features, Renal Function, and Cardiovascular Biomarkers

“…Similar conclusions were drawn by Verma and Dalal, who found that sCOMP was associated with pain but not radiological changes [16]. Furthermore, they described an overall negative association between the level of sCOMP and disease progression-an association which might be explained by the gradual depletion of interterritorial COMP found in human late-stage OA cartilage [19]. Nevertheless, Verma and Dalal proposed that sCOMP might serve as a prognostic marker, which allows determining patients at risk of rapid disease progression in the early stages of OA [16].…”

“…In the late stages of OA, the elevated synovial fluid and serum levels of COMP (sCOMP) are declining probably due to its depletion in highly degenerated tissue [16,18,19]. However, locally high expression was reported in chondrocytes adjacent to severely damaged cartilage, indicating a possible implication in insufficient repair processes [20].…”

Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis

“…In humans, chondrodysplasia-causing mutations in COMP, collagen IX, or MATN3 are frequently associated with premature osteoarthritis. Matrilin-3 is present at low levels in the joint articular surface and its deposition is upregulated in cartilage and in the synovial fluid of patients with OA as a consequence of cartilage degradation [56][57][58][59][60]. Studies with recombinant MATN3 and human primary chondrocytes have revealed that MATN3 exhibits a context-dependent anabolic or catabolic function by influencing the expression of pro-inflammatory cytokines, ECM degradation enzymes, and ECM synthesis [59,[61][62][63] through the modulation of protein kinase B (AKT) [59], interleukin-6 [62], and interleukin-1 [63,64] signaling pathways.…”

COMP in the Infrapatellar Fat Pad—Results of a Prospective Histological, Immunohistological, and Biochemical Case–Control Study

“…Furthermore, COMP interacts with growth factors, and besides regulating extracellular matrix composition and assembly, it also affects cellular functions such as proliferation, differentiation, and attachment of cells . Several studies have shown that the localization and expression of COMP differs between healthy hyaline articular cartilage and osteoarthritic cartilage . In addition, elevated serum COMP levels have been reported in OA, rheumatoid arthritis, and injured knees .…”

“…32 Several studies have shown that the localization and expression of COMP differs between healthy hyaline articular cartilage and osteoarthritic cartilage. 33 In addition, elevated serum COMP levels have been reported in OA, 34,35 rheumatoid arthritis, 36 and injured knees. 37 COMP has also been detected in human adipose tissue and there are differences in expression between abdominal fat and gluteal fat.…”