title: Thyroid hormones enhance the biomechanical functionality of scaffold-free neocartilage.
abstract: BACKGROUND
  The aim of this study was to investigate the effects of thyroid hormones tri-iodothyronine (T3), thyroxine (T4), and parathyroid hormone (PTH) from the parathyroid glands, known to regulate the developing limb and growth plate, on articular cartilage tissue regeneration using a scaffold-free in vitro model.
  
  
  METHODS
  In Phase 1, T3, T4, or PTH was applied during weeks 1 or 3 of a 4-week neocartilage culture. Phase 2 employed T3 during week 1, followed by PTH during week 2, 3, or weeks 2 to 4, to further enhance tissue properties. Resultant neotissues were evaluated biochemically, mechanically, and histologically.
  
  
  RESULTS
  In Phase 1, T3 and T4 treatment during week 1 resulted in significantly enhanced collagen production; 1.4- and 1.3-times untreated neocartilage. Compressive and tensile properties were also significantly increased, as compared to untreated and PTH groups. PTH treatment did not result in notable tissue changes. As T3 induces hypertrophy, in Phase 2, PTH (known to suppress hypertrophy) was applied sequentially after T3. Excitingly, sequential treatment with T3 and PTH reduced expression of hypertrophic marker collagen X, while yielding neocartilage with significantly enhanced functional properties. Specifically, in comparison to no hormone application, these hormones increased compressive and tensile moduli 4.0-fold and 3.1-fold, respectively.
  
  
  CONCLUSIONS
  This study demonstrated that T3, together with PTH, when applied in a scaffold-free model of cartilage formation, significantly enhanced functional properties. The novel use of these thyroid hormones generates mechanically robust neocartilage via the use of a scaffold-free tissue engineering model.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA. jele@ucdavis.edu.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA. cagegg@ucdavis.edu.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Gegg
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA. jcyhu@ucdavis.edu.
authors.forename: Jerry C
authors.initials: JC
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA. ahreddi@ucdavis.edu.
authors.forename: A Hari
authors.initials: AH
authors.lastname: Reddi
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA. athanasiou@ucdavis.edu.|Department of Orthopaedic Surgery, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA. athanasiou@ucdavis.edu.
authors.forename: Kyriacos A
authors.initials: KA
authors.lastname: Athanasiou
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology*; D002358:Cartilage, Articular / Q000502:physiology*; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects*; D066298:In Vitro Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D010281:Parathyroid Hormone; D014284:Triiodothyronine; D013974:Thyroxine