Christopher B. Little and Margaret M. Smith

Bio: Christopher B. Little and Margaret M. Smith is an academic researcher. The author has contributed to research in topics: Socioeconomic status & Medicine. The author has an hindex of 1, co-authored 1 publications receiving 90 citations.

Animal Models of Osteoarthritis

Abstract: The complex pathobiologic changes of human joint disease, particularly osteoarthritis (OA), normally take sev- eral decades to develop and may be influenced by a multitude of genetic and environmental factors. The need to clarify the molecular events that occur in joint tissues at the onset and during the progression of OA has necessitated the use of models, which, although imperfect, can exhibit many of the pathologic features that characterize the human disease. In vi- tro studies have proven invaluable in defining specific molecular and cellular events in degradation of joint tissues such as cartilage. However, to fully understand the complex inter-relationship between the different disease mechanisms, joint tis- sues and body systems, studying OA in animal models is necessary. Models of inflammatory arthropathies have proven predictive of clinical efficacy, with therapies that are beneficial in animals having significant benefit in treatment of rheumatoid arthritis in humans. While none of the available animal models of OA can truly be said to be predictive, as no anti-OA therapies have yet proven to be disease modifying in human trials, this approach represents a cornerstone for dis- covery of new anti-OA therapeutic targets and drugs. In this paper the available species and models of OA are reviewed and their potential utility discussed.

Post-traumatic osteoarthritis: from mouse models to clinical trials

Abstract: Osteoarthritis (OA), the most common of all arthropathies, is a leading cause of disability and has a large (and growing) worldwide socioeconomic cost. Despite its burgeoning importance, translation of disease-modifying OA therapies from the laboratory into clinical practice has slowed. Differences between the OA models studied preclinically and the disease evaluated in human clinical trials contribute to this failure. Most animal models of OA induce disease through surgical or mechanical disruption of joint biomechanics in young individuals rather than the spontaneous development of age-associated disease. This instability-induced joint disease in animals best models the arthritis that develops in humans after an injurious event, known as post-traumatic OA (PTOA). Studies in genetically modified mice suggest that PTOA has a distinct molecular pathophysiology compared with that of spontaneous OA, which might explain the poor translation from preclinical to clinical OA therapeutic trials. This Review summarizes the latest data on potential molecular targets for PTOA prevention and modification derived from studies in genetically modified mice, and describes their validation in preclinical therapeutic trials. This article focuses on how these findings might best be translated to humans, and identifies the potential challenges to successful implementation of clinical trials of disease-modifying drugs for PTOA.

A Review of Translational Animal Models for Knee Osteoarthritis

Abstract: Knee osteoarthritis remains a tremendous public health concern, both in terms of health-related quality of life and financial burden of disease. Translational research is a critical step towards understanding and mitigating the long-term effects of this disease process. Animal models provide practical and clinically relevant ways to study both the natural history and response to treatment of knee osteoarthritis. Many factors including size, cost, and method of inducing osteoarthritis are important considerations for choosing an appropriate animal model. Smaller animals are useful because of their ease of use and cost, while larger animals are advantageous because of their anatomical similarity to humans. This evidence-based review will compare and contrast several different animal models for knee osteoarthritis. Our goal is to inform the clinician about current research models, in order to facilitate the transfer of knowledge from the “bench” to the “bedside.”

Advances in Porous Scaffold Design for Bone and Cartilage Tissue Engineering and Regeneration.

Abstract: Tissue engineering of bone and cartilage has progressed from simple to sophisticated materials with defined porosity, surface features, and the ability to deliver biological factors. To avoid elici...