Abstract
IntroductionThe 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.MethodsIn 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.ResultsIn 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0541-5) contains supplementary material, which is available to authorized users.
Highlights
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
It was hypothesized that the application of these thyroid hormones to articular chondrocytes in an in vitro model of scaffold-free cartilage formation would induce matrix maturation and enhance matrix mechanical properties
It was hypothesized that scaffold-free neocartilage treated with T3 may exhibit markers of hypertrophy, but that sequential application of T3 and PTH would reduce hypertrophic marker expression
Summary
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. Surgical treatment options for patients with articular cartilage damage range from pain-alleviating microfracture techniques to end-stage total knee arthroplasty, with increasing numbers of developing therapies focused on avoiding joint replacement [1]. A scaffold-free tissue engineering approach, based on a self-assembling process, recapitulates cartilage development [4,5] and is amenable to the application of chemical and mechanical stimuli to drive cartilage matrix synthesis and maturation [6,7]. Application of exogenous agents can produce neocartilage with mechanical properties approaching those of native cartilage tissue; for example, stimulated self-assembled neocartilage can possess a compressive stiffness over 200 kPa [7], in range of native articular cartilage values [8]. Cartilage developmental biology has driven the identification of new stimuli suitable for use in the self-assembling process, toward better enhancing the mechanical and biochemical properties of engineered neocartilage
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