Animal Models of Osteoarthritis: Lessons Learned While Seeking the 'Holy Gr
Animal Models of Osteoarthritis: Lessons Learned While Seeking the 'Holy Gr
Purpose of Review: Difficulties in studying osteoarthritis in humans that stem from both the low sensitivity of diagnostic tools and the low availability of diseased tissues explain why research on animal models remains highly dynamic. This review will summarize the recent advances in this field.
Recent Findings: With regard to the etiology of osteoarthritis, synovial macrophages mediate osteophyte formation, whereas increased ligament laxity could be responsible for spontaneous osteoarthritis in guinea pigs. The concomitant changes in subchondral bone and cartilage reported in several models, and the structure-modifying effects of some bone inhibitors have confirmed the importance of bone in osteoarthritis. With regard to cartilage pathobiology, ADAMTS-5 is the major aggrecanase responsible for cartilage destruction, whereas inadequate control of oxidative stress and decreased expression of transforming growth factor-β receptors could predispose to osteoarthritis. New models include a postmenopausal rat model, the groove model and a joint-specific bone morphogenetic receptor-deficient mouse. The iodoacetate model was also validated as the first pain model of osteoarthritis.
Summary: In view of the multiple animal models available, there is a need to reach a consensus on one or several gold standard animal model(s). New studies indicate that important differences in therapeutic response exist between young and old animals, and between spontaneous and surgical models, suggesting that not all models are adequate models of osteoarthritis.
Animal models of osteoarthritis (OA) include spontaneous models in aging animals, genetically modified mice, as well as surgically, enzymatically or chemically induced models (see for recent reviews). Research on these models remains highly dynamic due to the difficulties in studying osteoarthritis in humans, which stem from poorly sensitive diagnostic tools and the low availability of diseased tissues. This review summarizes the recent advances in this field and underlines the impact of the major new findings on OA research.
Abstract and Introduction
Abstract
Purpose of Review: Difficulties in studying osteoarthritis in humans that stem from both the low sensitivity of diagnostic tools and the low availability of diseased tissues explain why research on animal models remains highly dynamic. This review will summarize the recent advances in this field.
Recent Findings: With regard to the etiology of osteoarthritis, synovial macrophages mediate osteophyte formation, whereas increased ligament laxity could be responsible for spontaneous osteoarthritis in guinea pigs. The concomitant changes in subchondral bone and cartilage reported in several models, and the structure-modifying effects of some bone inhibitors have confirmed the importance of bone in osteoarthritis. With regard to cartilage pathobiology, ADAMTS-5 is the major aggrecanase responsible for cartilage destruction, whereas inadequate control of oxidative stress and decreased expression of transforming growth factor-β receptors could predispose to osteoarthritis. New models include a postmenopausal rat model, the groove model and a joint-specific bone morphogenetic receptor-deficient mouse. The iodoacetate model was also validated as the first pain model of osteoarthritis.
Summary: In view of the multiple animal models available, there is a need to reach a consensus on one or several gold standard animal model(s). New studies indicate that important differences in therapeutic response exist between young and old animals, and between spontaneous and surgical models, suggesting that not all models are adequate models of osteoarthritis.
Introduction
Animal models of osteoarthritis (OA) include spontaneous models in aging animals, genetically modified mice, as well as surgically, enzymatically or chemically induced models (see for recent reviews). Research on these models remains highly dynamic due to the difficulties in studying osteoarthritis in humans, which stem from poorly sensitive diagnostic tools and the low availability of diseased tissues. This review summarizes the recent advances in this field and underlines the impact of the major new findings on OA research.
