Yet again, a non-endocrinological application of thyroid hormone - in this case levothyroxine (T4).
Interesting to know if there is anything specific about T4 - would T3 (in appropriate doses) have had the same effect?
Given the number of people who suffer joint and other collagen-related issues, simply identifying that there is a direct effect of thyroid hormone on collagen might be a major step in itself. I keep hoping that a comprehensive understanding of the actual effects of thyroid hormone at the fundamental biochemical level would help to support the numerous signs and symptoms reported by patients.
Tissue Eng Part A. 2017 May 26. doi: 10.1089/ten.TEA.2016.0533. [Epub ahead of print]
Thyroxine increases collagen type II expression and accumulation in scaffold-free tissue engineered articular cartilage.
Whitney GA1,2, Kean TJ3, Fernandes RJ4, Waldman SD5, Tse MY6, Pang SC7, Mansour JM8,9, Dennis JE10.
Author information
1 Benaroya Research Institute, Hope Heart Matrix Program, Seattle, Washington, United States.
2 Case Western Reserve University, Biomedical Engineering, Cleveland, Ohio, United States ; g.adam.whitney@gmail.com.
3 Baylor College of Medicine, Orthopedic Surgery, Houston, Texas, United States ; thomas.kean@bcm.edu.
4 University of Washington, Orthopedics, Seattle, Washington, United States ; rjf@uw.edu.
5 Ryerson University, Chemical Engineering, Toronto, Ontario, Canada ; swaldman@ryerson.ca.
6 Queen's University, 4257, Biomedical and Molecular Sciences, Kingston, Ontario, Canada ; yat.tse@queensu.ca.
7 Queen's University, 4257, Biomedical and Molecular Sciences, Kingston, Ontario, Canada ; pangsc@queensu.ca.
8 Case Western Reserve University, Department of Mechanical and Aerospace Engineering, Cleveland, Ohio, United States.
9 Case Western Reserve University, Department of Orthopaedics, Cleveland, Ohio, United States ; jmm12@case.edu.
10 Baylor College of Medicine, Orthopedic Surgery, Houston, Texas, United States ; james.dennis@bcm.edu.
Abstract
Low collagen accumulation in the extra-cellular matrix is a pressing problem in cartilage tissue engineering, leading to a low collagen-to-glycosaminoglycan (GAG) ratio and poor mechanical properties in neo-cartilage. Soluble factors have been shown to increase collagen content, but may result in a more pronounced increase in GAG content. Thyroid hormones have been reported to stimulate collagen and GAG production, but reported outcomes, including which specific collagen types are affected, are variable throughout the literature. Here we investigated the ability of thyroxine (T4) to preferentially stimulate collagen production, as compared to GAG, in articular chondrocyte-derived scaffold-free engineered cartilage. Dose response curves for T4 in pellet cultures showed that 25 ng/mL T4 increased the total collagen content without increasing the GAG content, resulting in a statistically significant increase in the collagen-to-GAG ratio, a fold change of 2.3±1.2, p<0.05. In contrast, another growth factor, TGFβ1, increased the GAG content in excess of three-fold more than the increase in collagen. In large scaffold-free neo-cartilage, T4 also increased the total collagen/DNA at one month and at two months (fold increases of 2.1±0.8, p<0.01 and 2.1±0.4, p<0.001, respectively). Increases in GAG content were not statistically significant. The effect on collagen was largely specific to collagen type II, which showed a 2.8±1.6 fold increase of COL2A1 mRNA expression (p<0.01). Western blots confirmed a statistically significant increase in type II collagen protein at one month (fold increase of 2.2±1.8); at two months, the fold increase of 3.7±3.3 approached significance (p=0.059). Collagen type X protein was below the 0.1 µg limit of detection. T4 did not affect COL10A1 and COL1A2 gene expression in a statistically significant manner. Biglycan mRNA expression increased 2.6±1.6 fold, p<0.05. Results of this study show that an optimized dosage of T4 is able to increase collagen type II content, and do so preferential to GAG. Moreover, the upregulation of COL2A1 gene expression and type II collagen protein accumulation, without a concomitant increase in collagens type I or type X, signifies a direct enhancement of chondrogenesis of hyaline articular cartilage without the induction of terminal differentiation.
PMID: 28548569
DOI: 10.1089/ten.TEA.2016.0533
ncbi.nlm.nih.gov/pubmed/285...
[ Edited 28/05/2017 08:35 ]
If the above paper was of interest, you might find one of its references worth reading - most especially as it it twenty years old and investigated both T4 and T3.
In serum-free culture thyroid hormones can induce full expression of chondrocyte hypertrophy leading to matrix calcification.
ncbi.nlm.nih.gov/pubmed/877...
Chondrocytes (from Greek χόνδρος, chondros = cartilage + κύτος, kytos = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans.
Thanks Wiki.