Does Cartilage Protein Distribution Vary Across Anatomical Regions of the Femur and Tibia in Osteoarthritic Knees?...

The aim of this study was to elucidate the difference in the protein distribution between anatomical regions of the femur and tibia in osteoarthritic knees in macroscopically uninvolved areas.

Proteomic analysis was performed on cartilage tissues isolated from femoral and tibial macroscopically uninvolved areas of the knees during total knee arthroplasty. Six samples were collected in each group. The proteomic analyses comprised extraction of soluble proteins from cartilage, separation of the protein mixtures followed by in-solution digestion, extracts were subjected to precipitation and subsequent tandem mass spectrometry analysis in conjunction with a database search for protein identification and semi-quantitation. Differential analysis was carried out using metaboanalyst software.

A total of 967 and 869 proteins were identified in femoral and tibial condyles, respectively. Based on stringent parameters (≥ 5 PSM, one unique peptide, 100% sample positivity), 183 common proteins were identified, of which four proteins showed significant differential expression (p < 0.05, fold change ≥ 1.5). Three proteins were downregulated in the femoral condyle: transthyretin (fold change: 3.04, log2FC: - 0.627 [95% CI - 1.12 to - 0.13], p = 0.0004), apolipoprotein A1 (fold change: 1.66, log2FC: - 0.58 [95% CI - 1.03 to - 0.13], p = 0.007), and alpha-2-macroglobulin (fold change: 1.7, log2FC: - 1.118 [95% CI - 2.35 to 0.11], p = 0.045). One protein, transketolase, was upregulated (fold change: 1.6, log2FC: 0.776 [95% CI 0.12-1.43], p = 0.01). Unique proteins of the femoral condyle were enriched in pathways crucial for chondrocyte metabolism and cartilage homeostasis. Tibial condyle proteins were enriched in complement and coagulation cascades (p < 0.01).

Proteomic analysis identified subtle yet meaningful differences in protein expression between the femoral and tibial condyles of osteoarthritic knees. The differences in biological process enrichment highlight the unique functional roles and regulatory mechanisms of the femoral and tibial condyles in controlling OA progression.