Analysis of the Inflammatory and Degenerative State of Osteoarthritic Joints

Abstract

Development of disease modifying osteoarthritis drugs has been hindered by an inability to diagnose osteoarthritis prior to structural changes and by animal models that cannot predict human responses to disease modifying interventions. The first part of this dissertation evaluated if a novel nonsurgical-voluntary animal model was capable of producing joint inflammation and degeneration as well as if ibuprofen could attenuate these outcomes. Spraque-Dawley rats were divided among 7 groups. The four experimental groups consisted of two trained to perform a high-repetition, high-force (HRHF) task without ibuprofen for 6 (N = 5) and 12 weeks (n = 16) and two trained to perform a HRHF task for 6 (N = 5) and 12 weeks (N = 16) with ibuprofen initiated at week 4 of the 12 week training protocol. Three groups served as controls: trained controls (N = 8), trained controls plus ibuprofen (N = 9), and normal controls that were not trained or provided ibuprofen (N = 13). Twelve weeks of the HRHF task produced joint inflammation and degeneration. Ibuprofen attenuated these outcomes. The second part of this dissertation evaluated if skin potentials were a noninvasive diagnostic marker for osteoarthritis. Skin and intra-articular potentials as well as synovial protein concentrations were measured in osteoarthritic (N = 4) and normal knees (N = 4). Skin potentials were not different between the groups but correlated to 7 synovial protein concentrations. Six synovial protein concentrations were significantly different between the groups. The HRHF task animal model induced joint inflammation and degeneration, and may be useful for assessing therapeutic and disease modifying responses to interventions. Future research needs to assess if this model is predictive of human responses to interventions. Although skin potentials may not differentiate between osteoarthritic and normal knees, they do relate to biochemical conditions within the knee. Future research needs to determine the mechanism that produces this relationship with the goal of improving measurement techniques to develop an early diagnostic marker for osteoarthritis. Development of new diagnostic markers for osteoarthritis and animal models for studying early osteoarthritis and disease modifying drugs represents the key to advancing disease modifying osteoarthritis drugs.