Recognition of Immune Response for the Early Diagnosis and Treatment of Osteoarthritis

Abstract

Osteoarthritis is a common and debilitating joint disease that affects up to 30 million Americans, leading to significant disability, reduction in quality of life, and costing the United States tens of billions of dollars annually. Classically, osteoarthritis has been characterized as a degenerative, wear-and-tear disease, but recent research has identified it as an immunopathological disease on a spectrum between healthy condition and rheumatoid arthritis. A systematic literature review demonstrates that the disease pathogenesis is driven by an early innate immune response which progressively catalyzes degenerative changes that ultimately lead to an altered joint microenvironment. It is feasible to detect this infiltration of cells in the early, and presumably asymptomatic, phase of the disease through noninvasive imaging techniques. This screening can serve to aid clinicians in potentially identifying high-risk patients, hopefully leading to early effective management, vast improvements in quality of life, and significant reductions in disability, morbidity, and cost related to osteoarthritis. Although the diagnosis and treatment of osteoarthritis routinely utilize both invasive and non-invasive strategies, imaging techniques specific to inflammatory cells are not commonly employed for these purposes. This review discusses this paradigm and aims to shift the focus of future osteoarthritis-related research towards early diagnosis of the disease process.

Figure 1

Complement synovial infiltration in the early pathogenesis of OA. ELISA quantification of C3a des-arginine in synovial fluid of healthy (n = 14), early-stage OA (n = 52), and end-stage OA (n = 69) patients. C3a des-arginine is a carboxypeptidase-cleaved, stable form of C3a that is generated from C3 during activation of the complement cascade. ^** P ≤ 0.01 by one-way analysis of variance (ANOVA) and Dunnett's post hoc test (reproduction of image with permission and modified caption from Wang et al. [17]).

Figure 2

In vivo imaging of inflammation with two cFLFLF-derived probes in the rat knee joints treated with (right knee) or without (left knee) monoiodoacetate (MIA). (a) CFLFLF-PEG-Cy 7 probe with animal back down, at day 5 after MIA injection; (b) cFLFLF-PEG-DOTA-⁶⁴Cu with animal back up, at day 5 after MIA injection (upper column: micro-CT; middle column: micro-PET; lower column: fused).

Figure 3

Inflammatory biomarkers in PET imaging (reproduced with permission from Wu et al. [99]).

Figure 4

Model for role of systemic proinflammatory state and OA. Inflammatory mediators released into blood enter the joint exacerbating OA, which releases its own mediators of inflammation leading to increased systemic inflammation (reproduced with permission from Berenbaum [6]).