title: The repair of full-thickness articular cartilage defect using intra-articular administration of N-acetyl-D-glucosamine in the rabbit knee: randomized controlled trial.
abstract: BACKGROUND
  Although various alterative models of therapy are used for cartilage repair, no definite conclusion has been reached. Glucosamine (GlcN) is widely used as a nutritional supplement. However, the clinical- evidence-based outcome of GlcN administration remains controversial. N-acetyl-D-glucosamine (GlcNAc), a derivative of GlcN, shows chondroprotective activity and mediates the activation of articular chondrocytes. Therefore, we investigated the effect of intra-articular administration of GlcNAc in rabbits' knee joints with experimental full-thickness articular cartilage (FTAC) defects.
  
  
  METHODS
  Twelve male adult New Zealand white rabbits, providing 24 knees, were used in this study. FTAC defects were created in the high-weight-bearing area of the medial femoral condyles of bilateral knees. All rabbits were randomly allocated to analysis at postsurgical week 4 or postsurgical week 12. In the week 4 group, rabbits' knees (six per group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 3 weeks, beginning 1 week postoperatively. In the week 12 group, the rabbits' knees (six in each group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 4 weeks, beginning 1 week postoperatively. Rabbits were sacrificed at 4 or 12 weeks after surgery for macroscopic, histological and radiological examinations of the knee joints.
  
  
  RESULTS
  All rabbits had no systemic or local adverse effects. The saline and GlcNAc groups showed visible differences in healing of the FTAC defect at the end of testing. At week 4, the GlcNAc group had a higher level of collagen type II (COL II) and showed up-regulated production of transforming growth factor (TGF)-β2 and TGF-β3, suggesting the involvement of endogenous growth factors. At week 12, the GlcNAc group displayed formation of hyaline-like cartilage regeneration with mature chondrocytes (SOX9+), robust glycosaminoglycan (GAG) content, and positive COL II content in both the adjacent cartilage and reparative sites. However, the saline group demonstrated mainly fibrocartilage scar tissue, indicating COL I expression. Furthermore, the GlcNAc group had significantly higher bone volume per tissue volume and higher trabecular thickness than the saline group.
  
  
  CONCLUSIONS
  Intra-articular GlcNAc may promote the repair of experimental FTAC defects in the rabbit knee joint model.
authors.affiliation: Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. mlyeh@mail.ncku.edu.tw.
authors.forename: Nai-Jen
authors.initials: NJ
authors.lastname: Chang
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, 1 University Rd., Tainan, 701, Taiwan. mlyeh@mail.ncku.edu.tw.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Laboratory Animal Center, Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan. mlyeh@mail.ncku.edu.tw.
authors.forename: Chih-Chan
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, 1 University Rd., Tainan, 701, Taiwan. mlyeh@mail.ncku.edu.tw.
authors.forename: Hsueh-Chun
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, China Medical University Hospital, Taichung, Taiwan. mlyeh@mail.ncku.edu.tw.
authors.forename: Horng-Chaung
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, 1 University Rd., Tainan, 701, Taiwan. mlyeh@mail.ncku.edu.tw.|Medical Device Innovation Center, National Cheng Kung University, Tainan, 701, Taiwan. mlyeh@mail.ncku.edu.tw.
authors.forename: Ming-Long
authors.initials: ML
authors.lastname: Yeh
mesh_terms: D000117:Acetylglucosamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D007267:Injections; D007719:Knee Joint / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D055114:X-Ray Microtomography
chemical_list: D000117:Acetylglucosamine