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

Abstract

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 (Cl 2 ) 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 Cl 2 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. ß

Hypochlorite-induced structural modifications enhance the chaperone activity of human α2-macroglobulin

“…Consistent with the idea that a large amount of hypochlorite may be generated in vivo during inflammation, extracellular myeloperoxidase is also estimated to reach millimolar concentrations (33), and using computational modeling, it is predicted that proteins from atherosclerotic plaques are exposed to a 20-fold molar excess of hypochlorite over their lifetime (32). In addition, it is very clear that proteins are modified by hypochlorite in vivo and that the extent of these modifications is increased in many disease states, including atherosclerosis (40), Alzheimer's disease (5), kidney disease (49), rheumatoid arthritis (45), osteoarthritis (50), and chronic lung disease (51).…”

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“…Recently, Marla J. Steinbeck et al 1 showed that HOCl and Cl 2 oxidize pyridinoline (PYD) compounds to form chlorinated moieties 6 . PYD crosslinks are integral members in the structural composition of articular cartilage that serve to covalently link helical regions of Col-II to one another, type IX collagen (Col-IX) to the surface of Col-II, and Col-IX to other molecules of Col-IX.…”

“…Recently in a study Patients with early OA demonstrated significantly elevated levels of MPO in synovial fluid 1 . Patients in the control and advanced OA groups demonstrated little elevation in MPO levels.…”

Arthritis Identification from Multiple Regions by X-Ray Image Processing

“…Steinbeck, 2007). According to World Health Organization (WHO) osteoarthritis is a serious disabling disease, statistically 1 in 10 developed countries are under its influence.…”