Progression of Cartilage Degradation, Bone Resorption and Pain in Rat Temporomandibular Joint Osteoarthritis Induced by Injection of Iodoacetate Xue-Dong Wang 1 , Xiao-Xing Kou 1 , Dan-Qing He 1 , Min-Min Zeng 1 , Zhen Meng 2 , Rui-Yun Bi2, Yan Liu1, Jie-Ni Zhang 1 , Ye-Hua Gan2*, Yan-Heng Zhou 1 * 1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China, 2 Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing, China Abstract Background: Osteoarthritis (OA) is an important subtype of temporomandibular disorders. A simple and reproducible animal model that mimics the histopathologic changes, both in the cartilage and subchondral bone, and clinical symptoms of temporomandibular joint osteoarthritis (TMJOA) would help in our understanding of its process and underlying mechanism. Objective: To explore whether injection of monosodium iodoacetate (MIA) into the upper compartment of rat TMJ could induce OA-like lesions. Methods: Female rats were injected with varied doses of MIA into the upper compartment and observed for up to 12 weeks. Histologic, radiographic, behavioral, and molecular changes in the TMJ were evaluated by light and electron microscopy, MicroCT scanning, head withdrawal threshold test, real-time PCR, immunohistochemistry, and TUNEL assay. Results: The intermediate zone of the disc loosened by 1 day post-MIA injection and thinned thereafter. Injection of an MIA dose of 0.5 mg or higher induced typical OA-like lesions in the TMJ within 4 weeks. Condylar destruction presented in a time-dependent manner, including chondrocyte apoptosis in the early stages, subsequent cartilage matrix disorganization and subchondral bone erosion, fibrosis, subchondral bone sclerosis, and osteophyte formation in the late stages. Nociceptive responses increased in the early stages, corresponding to severe synovitis. Furthermore, chondrocyte apoptosis and an imbalance between anabolism and catabolism of cartilage and subchondral bone might account for the condylar destruction. Conclusions: Multi-level data demonstrated a reliable and convenient rat model of TMJOA could be induced by MIA injection into the upper compartment. The model might facilitate TMJOA related researches. Citation: Wang X-D, Kou X-X, He D-Q, Zeng M-M, Meng Z, et al. (2012) Progression of Cartilage Degradation, Bone Resorption and Pain in Rat Temporomandibular Joint Osteoarthritis Induced by Injection of Iodoacetate. PLoS ONE 7(9): e45036. doi:10.1371/journal.pone.0045036 Editor: Andre Van Wijnen, University of Massachusetts Medical, United States of America Received June 2, 2012; Accepted August 11, 2012; Published September 11, 2012 Copyright: 2012 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This project is supported by the National Natural Science Foundation of China (Grant No. 81070849) and China International Science and Technology Cooperation (Grant No. 2010DFB32980). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: kqyehuagan@bjmu.edu.cn (YHG); yanhengzhou@gmail.com (YHZ) Introduction Temporomandibular joint osteoarthritis (TMJOA) is an impor- tant subtype of temporomandibular disorders (TMD) [1,2] and is especially common in female patients with severe pain and dysfunction of the temporomandibular joint (TMJ) [3,4]. OA is characterized by a progressive degradation of cartilage, subchon- dral bone remodeling, synovitis, and chronic pain [3,5,6]. However, the process of TMJOA remains obscure. Chondro- cyte death due to either apoptosis or necrosis is assumed to be a central feature in the degeneration of osteoarthritic cartilage and to contribute to the development of clinical or experimental OA [7,8]. Resorption and abrasion of condylar subchondral bone are unique in TMJOA, which usually shows no typical pannus in the synovium whereas rheumatoid arthritis does [3]. Therefore, a proper animal model may provide a useful way to understand the pathogenesis of TMJOA and to evaluate potential therapeutic interventions [9]. Thus far, several methods have attempted to create animal models of TMJOA, including surgical [10], mechanical [11], drug- inducing [12,13], and spontaneously occurring methods [14]. Due to the limited availability of special animal species, slow progression of the disease, and complicated operations, the use of spontaneous or surgical-induced methods was limited [13,15]. In addition, the lack of progressive changes led to a number of drug-induced models being merely models of cartilage damage rather than OA [9]. A simple and reproducible animal model of PLOS ONE | www.plosone.org 1 September 2012 | Volume 7 | Issue 9 | e45036