Insulin and Thyroid Hormones Stimulate Matrix Metabolism in Primary Cultures of Articular Chondrocytes from Young Rabbits Independently and in Combination

Glade, Michael J.; Kanwar, Yasphal S.; Stern, Paula H.

doi:10.3109/03008209409005633

Cited by 17 publications

(7 citation statements)

References 36 publications

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“…Other researchers have seen similar effects using T3 and T4, with T3 being a more potent inducer of collagen production [46,47]. However, these two studies did not observe an increase in hypertrophic markers such as COL10 and COL1, and this could be due to the cell type and concentration used in their experiments.…”

Section: Discussionmentioning

confidence: 71%

Human Osteochondral Explants: Reliable Biomimetic Models to Investigate Disease Mechanisms and Develop Personalized Treatments for Osteoarthritis

et al. 2021

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Introduction Likely due to ignored heterogeneity in disease pathophysiology, osteoarthritis (OA) has become the most common disabling joint disease, without effective disease-modifying treatment causing a large social and economic burden. In this study we set out to explore responses of aged human osteochondral explants upon different OA-related perturbing triggers (inflammation, hypertrophy and mechanical stress) for future tailored biomimetic human models. Methods Human osteochondral explants were treated with IL-1β (10 ng/ml) or triiodothyronine (T3; 10 nM) or received 65% strains of mechanical stress (65% MS). Changes in chondrocyte signalling were determined by expression levels of nine genes involved in catabolism, anabolism and hypertrophy. Breakdown of cartilage was measured by sulphated glycosaminoglycans (sGAGs) release, scoring histological changes (Mankin score) and mechanical properties of cartilage. Results All three perturbations (IL-1β, T3 and 65% MS) resulted in upregulation of the catabolic genes MMP13 and EPAS1 . IL-1β abolished COL2A1 and ACAN gene expression and increased cartilage degeneration, reflected by increased Mankin scores and sGAGs released. Treatment with T3 resulted in a high and significant upregulation of the hypertrophic markers COL1A1 , COL10A1 and ALPL . However, 65% MS increased sGAG release and detrimentally altered mechanical properties of cartilage. Conclusion We present consistent and specific output on three different triggers of OA. Perturbation with the pro-inflammatory IL-1β mainly induced catabolic chondrocyte signalling and cartilage breakdown, while T3 initiated expression of hypertrophic and mineralization markers. Mechanical stress at a strain of 65% induced catabolic chondrocyte signalling and changed cartilage matrix integrity. The major strength of our ex vivo models was that they considered aged, preserved, human cartilage of a heterogeneous OA patient population. As a result, the explants may reflect a reliable biomimetic model prone to OA onset allowing for development of different treatment modalities. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00287-y.

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Section: Discussionmentioning

confidence: 71%

Human Osteochondral Explants: Reliable Biomimetic Models to Investigate Disease Mechanisms and Develop Personalized Treatments for Osteoarthritis

et al. 2021

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“…Redifferentiation of dedifferentiated chondrocytes has been attempted by the addition of various cytokines, such as insulin, 34 triiodothyronine, 35 bone morphogenetic protein-2, Type II collagen was probed with a specific antibody at 4 weeks after implantation. Scale bar: 100 mm.…”

Section: Discussionmentioning

confidence: 99%

Identification of cartilage progenitor cells in the adult ear perichondrium: utilization for cartilage reconstruction

Togo

Utani

Naitoh

et al. 2006

Laboratory Investigation

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For cartilage reconstruction, it is still difficult to obtain a sufficient volume of cartilage and to maintain its functional phenotype for a long period. Utilizing tissue stem cells is one approach to overcome such difficulties. We show here the presence of cartilage progenitor cells in the ear perichondrium of adult rabbits by 5-bromo-2 0 -deoxyuridine labeling, clonogenicity, and differentiation analyses. Long-term label-retaining cells were demonstrated in the perichondrium. Cells from the perichondrium, that is, perichondrocytes were mechanically isolated using a raspatory and maintained in D-MEM/F-12 medium with 10% FCS. They proliferated more vigorously than chondrocytes from the cartilage. Perichondrocytes could differentiate into adipocytes as well as osteocytes in differentiation induction medium. For cartilage reconstruction in vivo, perichondrocytes were seeded on collagen sponge scaffolds and implanted in nude mice. After 4 weeks, the composites with perichondrocytes generated the same weight of cartilaginous tissue as those with chondrocytes. They produced glycosaminoglycan and type II collagen as shown by RT-PCR and immunohistochemical examination. On the contrary, rabbit bone marrow mesenchymal stem cells used as control could regenerate significantly smaller cartilage than perichondrocytes in the implant study. Based on these findings, we propose that the perichondrium containing tissue progenitor cells is one of the potential candidates for use in reconstructing cartilage and new therapeutic modalities.

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“…A concentration of 100 ng/mL was chosen to maximize the potential of a cellular response [11,22,23]. Phase 2 evaluated the use of 25 ng/mL PTH during week 2 (that is, daily for days 8 to 14), week 3 (that is, daily for days 15 to 21), or weeks 2 to 4 (that is, daily for days 8 to 28) sequentially after 0 or 100 ng/mL T3 application during week 1.…”

Section: Methodsmentioning

confidence: 99%

Thyroid hormones enhance the biomechanical functionality of scaffold-free neocartilage

Lee¹,

Gegg²,

Hu³

et al. 2015

Arthritis Res Ther

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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.

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Insulin and Thyroid Hormones Stimulate Matrix Metabolism in Primary Cultures of Articular Chondrocytes from Young Rabbits Independently and in Combination

Cited by 17 publications

References 36 publications

Human Osteochondral Explants: Reliable Biomimetic Models to Investigate Disease Mechanisms and Develop Personalized Treatments for Osteoarthritis

Human Osteochondral Explants: Reliable Biomimetic Models to Investigate Disease Mechanisms and Develop Personalized Treatments for Osteoarthritis

Identification of cartilage progenitor cells in the adult ear perichondrium: utilization for cartilage reconstruction

Thyroid hormones enhance the biomechanical functionality of scaffold-free neocartilage

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