title: Prostaglandin E2 receptor type 2-selective agonist prevents the degeneration of articular cartilage in rabbit knees with traumatic instability.
abstract: BACKGROUND
  Osteoarthritis (OA) is a common cause of disability in older adults. We have previously reported that an agonist for subtypes EP2 of the prostaglandin E2 receptor (an EP2 agonist) promotes the regeneration of chondral and osteochondral defects. The purpose of the current study is to analyze the effect of this agonist on articular cartilage in a model of traumatic degeneration.
  
  
  METHODS
  The model of traumatic degeneration was established through transection of the anterior cruciate ligament and partial resection of the medial meniscus of the rabbits. Rabbits were divided into 5 groups; G-S (sham operation), G-C (no further treatment), G-0, G-80, and G-400 (single intra-articular administration of gelatin hydrogel containing 0, 80, and 400 μg of the specific EP2 agonist, ONO-8815Ly, respectively). Degeneration of the articular cartilage was evaluated at 2 or 12 weeks after the operation.
  
  
  RESULTS
  ONO-8815Ly prevented cartilage degeneration at 2 weeks, which was associated with the inhibition of matrix metalloproteinase-13 (MMP-13) expression. The effect of ONO-8815Ly failed to last, and no effects were observed at 12 weeks after the operation.
  
  
  CONCLUSIONS
  Stimulation of prostaglandin E2 (PGE2) via EP2 prevents degeneration of the articular cartilage during the early stages. With a system to deliver it long term, the EP2 agonist could be a new therapeutic tool for OA.
authors.affiliation: Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Mitsui
authors.forename: Tomoki
authors.initials: T
authors.lastname: Aoyama
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Furu
authors.forename: Kinya
authors.initials: K
authors.lastname: Ito
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Jin
authors.forename: Takayuki
authors.initials: T
authors.lastname: Maruyama
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kanaji
authors.forename: Shinsei
authors.initials: S
authors.lastname: Fujimura
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sugihara
authors.forename: Akio
authors.initials: A
authors.lastname: Nishiura
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Junya
authors.initials: J
authors.lastname: Toguchida
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000293:injuries* / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D007718:Knee Injuries / Q000473:pathology* / Q000517:prevention & control*; D008863:Microspheres; D011453:Prostaglandins / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D011897:Random Allocation; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists* / Q000502:physiology
chemical_list: D011453:Prostaglandins; D058307:Receptors, Prostaglandin E, EP2 Subtype