Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions.

摘要: OBJECTIVE: Articular cartilage degeneration in osteoarthritis (OA) involves excessive degradation of extracellular matrix (ECM) and chondrocyte differentiation (hypertrophy). We determined the interrelationship between extent collagen cleavage by collagenase, degeneration, related gene expression patella-femoral condylar cartilages patients bearing very early focal OA-like articular lesions. METHODS: specimens with lesions adjacent normal from 3 donors were removed at autopsy as full-depth slices cut femoral condyle surface that articulates patella. Slices divided into sections used for Mankin grading, examination collagenase type II ELISA, RT-PCR. RESULTS: Early was associated increased collagen. The collagenases metalloproteinase-1 (MMP-1), MMP-14 (MT1-MMP), aggrecanase ADAMTS-5 (a disintegrin metalloprotease thrombospondin motifs) (but not ADAMTS-4); cytokines interleukin 1alpha/beta tumor necrosis factor-alpha (TNF-alpha); terminal differentiation-related genes COL10A1, MMP-13, MMP-9, Indian hedgehog; caspase often upregulated vicinity lesion. Growth factors growth plate proliferation, namely fibroblast factor-2, parathyroid hormone protein, transforming factor (TGF)-beta1/2, well molecules COL2A1 aggrecan expressed to remote Of all only exclusively seen association these Elevation activity a frequent elevation 3, IL-1alpha/beta, MMP-1, ADAMTS-5, decreased Sox-9 (SRY-type high-mobility-group box transcription factor-9), TGF-beta1, TGF-beta2, TNF-alpha, aggrecan. Other showed no observable difference changes activity. CONCLUSION: Very knee is accompanied upregulation degradation. Thus may be closely development such occurs OA.