Does the cartilage proteome differ between osteoarthritic knees with varus and valgus deformities? Insights from proteomic analysis.

PURPOSE: To elucidate the proteome profile of cartilage tissue with two distinct phenotypes namely varus and valgus osteoarthritic (OA) knees in response to different loading conditions. METHODS: Global proteomic analysis was performed on cartilage tissues isolated from weight-bearing and non-weight-bearing regions of varus (OA-varus) and valgus (OA-valgus) knees. The study group consists of eight samples in each category. Insolution digested cartilage tissue extracts were subjected to Q-exactive plus orbitrap quadrupole mass spectrometer for protein identifications. Downstream bioinformatic analysis were carried out to detect the altered proteins and pathways in OA-valgus and OA-varus groups. RESULTS: Mass spectrometric analysis revealed that 645 and 742 proteins were identified from OA-valgus and OA-varus respectively. The differential analysis showed that 44 proteins were up regulated and 29 proteins were down regulated in OA-varus after assigning sample cutoff to 50 %. SOD2 was the top up regulated protein (log2FC = 2.688) and serum amyloid protein SAA2-SAA4 was the top down regulated protein (log2FC = -1.983) in OA-varus. KEGG pathway analysis revealed that upregulated proteins and unique proteins of OA-varus were enriched for complement and coagulation cascade and regulation of actin cytoskeleton. While the downregulated proteins of OA-varus (i.e. upregulation in OA-valgus) and unique proteins of OA-valgus were enriched for metabolic pathways including glycolysis, cholesterol metabolism, etc. Further GO analysis revealed that OA-varus proteins were enriched for immune responses and OA-valgus proteins were enriched for ECM related functions. CONCLUSION: Distinct proteomic profiles between OA-valgus and OA-varus knees were identified, with immune response pathways prominently in varus knees, and metabolic and structural pathways predominantly in valgus knees. These findings can inform targeted therapeutic strategies and OA management.