Abstract
BACKGROUND: Knee osteoarthritis is a common degenerative joint disease involving multiple pathological processes, including energy metabolism, cartilage repair, and osteogenesis. To investigate the alterations in critical metabolic pathways and differential proteins in osteoarthritis patients through metabolomic and proteomic analyses and to explore the potential mechanisms underlying synovial osteogenesis during osteoarthritis progression. METHODS: Metabolomics was used to analyze metabolites in the synovial fluid and synovium of osteoarthritis patients (osteoarthritis group: 10; control group: 10), whereas proteomics was used to examine differential protein expression. Alkaline phosphatase activity was assessed to evaluate osteogenesis. RESULTS: Upregulation of the tricarboxylic acid cycle: Significant upregulation of the tricarboxylic acid cycle in the synovial fluid and synovium of osteoarthritis patients indicated increased energy metabolism and cartilage repair activity. Arginine metabolism and collagen degradation: Elevated levels of ornithine, proline, and hydroxyproline in the synovial fluid reflect active collagen degradation and metabolism, contributing to joint cartilage breakdown. Abnormal Phenylalanine Metabolism: Increased phenylalanine and tyrosine metabolite levels in osteoarthritis patients suggest their involvement in cartilage destruction and osteoarthritis progression. Synovial osteogenesis: Increased expression of type I collagen in the synovium and elevated alkaline phosphatase activity confirmed the occurrence of osteogenesis, potentially driven by the differentiation of synovial fibroblasts, mesenchymal stem cells, and hypertrophic chondrocytes. Relationships between differential proteins and osteogenesis: FN1 and TGFBI are closely associated with synovial osteogenesis, while the upregulation of energy metabolism pathways provides the energy source for osteogenic transformation. CONCLUSIONS: Alterations in energy metabolism, cartilage repair, and osteogenic mechanisms are critical. The related metabolites and proteins have potential as diagnostic and therapeutic targets for osteoarthritis.