Differential Proteome of Articular Chondrocytes From Patients with Osteoarthritis

Abstract

Cartilage damage is a major problem in osteoarthritis (OA). To gain insight into the pathogenesis of OA, we have analyzed the differential proteome of articular chondrocytes from these patients. Protein extracts were prepared from cultured chondrocytes from 6 patients with end-stage OA and 6 normal donors and were analyzed by 2D-DIGE. Differentially expressed proteins were identified by mass spectrometry (MS). Significant differential expression was observed for 27 proteins, with 14 underexpressed and 13 overexpressed chondrocyte OA proteins. Of special interest was the identification of destrin, cofilins, gelsolin, annexin A2, glycolytic enzymes, chaperones, cathepsin D, proteasome beta 9 subunit isoform 2 proprotein and proteasome activator hPA28 subunit beta. The altered expression of these proteins is consistent with events such as cytoskeleton binding, protein disruption, apoptosis, and glycolysis, demonstrating the ability of the 2D-DIGE/MS platform to identify proteins with altered expression in chondrocytes from patients with end-stage OA. The identification of these proteins may open new lines of research for this disease.

Effects of laser treatment on the expression of cytosolic proteins in the synovium of patients with osteoarthritis

“…Campbell et al found that cofilin expression was significantly upregulated in chondrocytes upon mechanical stress. Rollín et al performed differential proteomic investigation of chondrocytes in OA patients. The expression of cytoskeletal binding proteins including cofilin and annexin 2 significantly increased in OA chondrocytes.…”

Proteomic analysis of articular cartilage vesicles from normal and osteoarthritic cartilage

“…The presence of complements and immunoglobulins in OA ACVs warrants further consideration. While proteomic techniques would seem a logical methodology to investigate important changes in cartilage proteins in OA, cartilage is quite refractory to 2‐dimensional gel‐based protein analysis (40). This is due to the high concentrations of strongly charged proteoglycans which run anomalously on sodium dodecyl sulfate polyacrylamide gels, and to the highly crosslinked state of cartilage matrix, which is typically not soluble in sample buffers (41).…”

Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function

“…Thus, in OA, CHs cytoskeletal changes include both actin depolymerizing and polymerizing proteins and appear to lead to an overall actin polymerization increase ( Figure 5). Cytoskeletal differences between healthy and osteoarthritis (OA) hCHs were detected for tubulin, vinculin, gelsolin, destrin, cofilin-1, and cofilin-2 [205]. Due to the increase in the latter and its higher actin assembly activity [206], presumably causing overall enhanced F-actin, results in elevated cell elastic moduli.…”

“…Finally, a proteome analysis of knee AC hCHs derived from healthy vs. OA donors found that the expression of the actin-depolymerizing proteins destrin and cofilin-1 were downregulated in OA hCHs, whereas the expression of cofilin-2 and gelsolin, also actin-depolymerizing proteins, was upregulated in OA hCHs [ 205 ]. This is interesting because cofilin-2 has a weaker actin filament depolymerization activity than cofilin-1 and promotes F-actin assembly rather than disassembly in steady-state assays [ 206 ].…”