Myeloperoxidase and chlorinated peptides in osteoarthritis: potential biomarkers of the disease

Osteoarthritis (OA) is a disabling condition in which multiple initiating events or conditions (heritable and nonheritable) result in eventual loss of articular cartilage. However, the etiology of OA remains poorly understood, and diagnosis of early disease is difficult due to the lack of specific identifiers. Recent literature suggests that a series of inflammatory processes may be involved in initiating and propagating OA. We hypothesized that products of neutrophils and macrophages, namely myeloperoxidase (MPO), a specific enzyme responsible for the production of both highly reactive hypochlorous acid (HOCl) and chlorine gas (Cl₂) and chlorinated peptides, may be present in the synovial fluid of patients with OA. We examined the synovial fluid from 30 patients to identify and profile the presence of MPO. We divided the samples into three groups using radiographic and clinical assessment: (1) control, patients with acute knee injury with no history of OA and no radiographic evidence of OA; (2) early OA, patients with a mild OA based on radiographs; and (3) late OA, patients with a longstanding history of OA and with radiographic evidence of complete joint loss. Patients with early OA demonstrated significantly elevated levels of MPO. We also demonstrated the presence of HOCl and Cl₂ modified proteins (Cl‐peptides) in early OA synovial fluid samples by liquid chromatography and mass spectrometry. Patients in the control and advanced OA groups demonstrated little elevation in MPO levels and Cl‐peptides were undetectable. These results indicate that MPO and Cl‐peptides may serve as diagnostic markers for the detection of early OA.