[Frontiers in Bioscience E4, 74-100, January 1, 2012]

Osteoarthritis: genetic factors, animal models, mechanisms, and therapies

Qin Bian123, Yong-Jun Wang12 Shu-fen Liu12, Yi-Ping Li4

1Department of Orthopedics and Traumatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No.725 South Wan-ping Road, Shanghai, China, 200032, 2Institute of Spine, Shanghai University of Traditional Chinese Medicine, No.725 South Wan-ping Road, Shanghai, China, 200032, 3Institute of integrated Traditional Chinese Medicine and Western Medicine, Huashan Hospital, Fudan University, No.12 Middle Wu lu mu qi Road, Shanghai, China, 200040, 4Department of Pathology, University of Alabama at Birmingham, SHEL 810, 1825 University Blvd,Birmingham AL 35294-2182

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Genetic factors
3.1. Cartilage ECM structural genes
3.2. Bone mass related genes
3.3. Inflammation related genes
3.4. Other loci variants
4. Animal models
4.1. Genetically modified models
4.1.1. Factitious models
4.1.2. Spontaneous models
4.2 .Experimentally induced models
4.2.1. Biomechanical factor
4.2.2. Structural factor
5. Mechanisms
5.1. Cellular changes
5.2. Molecular changes
5.3. BMPs
5.3.1. BMPs and articular cartilage
5.3.2. BMPs and subchondral bone
5.3.3. BMPs and synovium
5.3.4. BMPs and repair
5.3.5. Others
6. Therapies
6.1. Clinical therapy
6.1.1. Global treatments
6.1.2. Local treatments
6.2. Preclinical therapy
6.2.1. Anticytokine/cytokine therapy
6.2.2. Gene therapy
6.2.3. Tissue/Cell transplantation
7. Summary and future directions
8. Acknowledgments
9. References

1. ABSTRACT

Osteoarthritis (OA) is the most common form of joint disease. OA frequently affects knees, hips, hands, and the spine. It is characterized by the progressive destruction of articular cartilage and subchondral bone accompanied by low-grade inflammation that together result in pain and deformity. Recent studies have shed light on the nature of OA genetic susceptibility and confirmed a number of candidate genes involved in the destruction of the synovium, articular cartilage, and subchondral bone in OA pathogenesis. During the progression of OA, there are several cellular changes in joints, including an increase in the number of activated osteoclasts and macrophages and an infiltration of the synovium by activated T-cells and B-cells. Pro-inflammatory mediators (e.g. interleukin IL-1, IL-1beta, IL-6, IL-17, and IL-18, and Tumor necrosis actor-alpha), proteinases (e.g. matrix metalloproteinase 9 and cathepsin K), and regulators of cartilage and bone formation (e.g. BMPs) have been shown to have important roles in OA progression at the molecular level. Studies have suggested that OA shares several common characteristics with rheumatoid arthritis (RA). To systematically understand OA, this review summarizes OA disease genes, mouse models of human disease experimental mouse models, mechanisms of OA pathogenesis, and current OA therapies.