Decreased Synovial Fluid α-Melanocyte-Stimulating-Hormone (α-MSH) Levels Reflect Disease Severity in Patients with Posttraumatic Ankle Osteoarthritis

Background: alpha-Melanocyte-stimulating hormone (alpha-MSH), an endogenous melanocortin peptide, has been demonstrated to have anti-inflammation effects and protect against cartilage damage. Objective In this study, we aimed to investigate whether alpha-MSH in ankle joint synovial fluid is associated with the disease severity of posttraumatic ankle osteoarthritis (PTAOA). Methods: 66 PTAOA patients undergoing ankle arthroscopical debridement or ankle joint replacement were enrolled in the study. Synovial fluid alpha-MSH concentrations were explored by a special radioimmunoassay method. Cartilage degradation biomarkers such as collagen type II (CTX-II), aggrecan-1 (AGG-1), as well as inflammatory markers, interleukin-6 (IL-6) and matrix metalloproteinases-3 (MMP-3) in the synovial fluid were determined by enzyme-linked immunosorbent assay (ELISA). The symptomatic and functional severity was evaluated using Teeny-Wiss scoring and AOFAS ankle-hindfoot rating scale. The radiographic progression of PTAOA was identified according to the modified ankle osteoarthritis Kellgren-Lawrence (KL) grading system. The modified Man kin score was used for assessing the histopathological severity for cartilage lesions. Receiver operating characteristic (ROC) curve was conducted and the area under curve (AUC) was used to the evaluate the diagnostic value of alpha-MSH levels for the prediction of the modified K-L grading by comparing with other biomarkers examined. Results: alpha-MSH levels in synovial fluid showed a negative correlation with, modified ankle K-L grading, Mankin scores, and degradation biomarkers CTX-II and AGG-1, as well as inflammation markers IL-6 and MMP-3. In addition, alpha-MSH levels were also positively associated with Teeny-Wiss scoring and AOFAS ankle-hindfoot scores. The AUC area of alpha-MSH was similar to CTX-II, AGG-1, IL-6, and MMP-3. Conclusions: Synovial fluid alpha-MSH levels showed an independent and negative correlation with disease severity in patients with PTAOA. Application of alpha-MSH locally may serve as a potential adjuvant therapy for delaying the process of PTAOA.