Thyroid hormones enhance the biomechanical functionality of scaffold-free neocartilage

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.

Transthyretin deposition promotes progression of osteoarthritis

“…However, our results suggest that there may be effects of TTR deficiency on articular cartilage that may result in increased susceptibility to OA in the setting of induced joint damage. The role of thyroid hormones in regulating hypertrophic chondrocyte differentiation is well known (Williams, ), and recent studies indicate that thyroxin for which TTR functions as a carrier protein stimulated cartilage formation in mesenchymal stem cells (Lee et al ., ). However, only limited information is available on the role of thyroxine in articular chondrocytes (Rosenthal et al ., ).…”

Tension stimulation drives tissue formation in scaffold-free systems

“…Articular chondrocytes were harvested from the distal femur of juvenile bovine joints (Research 87, Boston, MA) as previously described 52 . Neocartilage was formed using the self-assembling process 53 at a seeding density of 8 million cells in 100μL of chondrogenic medium (CHG) 52 per 13×8mm construct. Human articular chondrocytes were obtained from three Caucasian, male donors, ages 19, 21, and 43, with no known musculoskeletal pathology (Musculoskeletal Transplant Foundation, Kansas City, MO).…”

“…Tensile and compressive tests (n=6 per group) and biochemical evaluation (n=6 per group) for collagen, sulfated GAG, and DNA content were performed as previously described 52 . Dumbbell-shaped tensile test samples were obtained in the direction parallel and perpendicular to the axis of tension stimulation and as indicated in Figure 1e and Supplemental Figure 1a .…”

Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

“…PTH had been widely investigated for treating osteoporosis by adopting various delivery strategies such as injections, oral dosing, pulmonary inhalation, and transdermal delivery. But, most of these studies were focused on systemic delivery of PTH, whereas relatively few studies have looked at local delivery of PTH (1–34) [ 22 , 23 ]. Systemic administration of PTH does not allow maintenance of therapeutic concentrations over time.…”

“…Consequently, continuous inhalations were required for achieving and maintaining effective concentrations. Alternatively, various strategies have been investigated to modulate PTH concentrations PLGA microspheres incorporated PTH (1–34) that were developed for local delivery [ 23 ]. The resultant microspheres sustained delivery of PTH from microparticles for more than 11 weeks.…”