title: Progression of cartilage degradation, bone resorption and pain in rat temporomandibular joint osteoarthritis induced by injection of iodoacetate.
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.
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Wang
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Kou
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: He
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Zeng
authors.forename: Zhen
authors.initials: Z
authors.lastname: Meng
authors.forename: Rui-Yun
authors.initials: RY
authors.lastname: Bi
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Jie-Ni
authors.initials: JN
authors.lastname: Zhang
authors.forename: Ye-Hua
authors.initials: YH
authors.lastname: Gan
authors.forename: Yan-Heng
authors.initials: YH
authors.lastname: Zhou
mesh_terms: D000477:Alkylating Agents / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018771:Arthralgia / Q000139:chemically induced*; D001862:Bone Resorption / Q000139:chemically induced*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007267:Injections; D007461:Iodoacetates / Q000008:administration & dosage / Q000633:toxicity*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D010003:Osteoarthritis / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013704:Temporomandibular Joint / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D000477:Alkylating Agents; D007461:Iodoacetates; D053148:Caspase 3; D019278:Matrix Metalloproteinase 3