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An Ex vivo Culture System to Study Thyroid Development
Published on: June 6, 2014
Postnatal development of dependence on thyroid hormones for growth and differentiation of rat skeletal structures
Insights
Thyroid hormones are crucial for skeletal development in rats. Endochondral bones require thyroid hormone (TH) earlier than membranous bones for growth and differentiation.
Area of Science:
- Endocrinology
- Developmental Biology
- Orthopedics
Background:
- Thyroid hormones (TH) play a vital role in mammalian growth and development.
- The precise timing of skeletal tissue dependence on TH is not fully understood.
Purpose of the Study:
- To investigate the developmental timeline of thyroid hormone dependence for the growth and differentiation of various rat skeletal tissues.
- To compare the TH dependence between endochondral bones, membranous bones, and cartilage.
Main Methods:
- Transplantation of neonatal rat skeletal tissues (radius, sternum, calvarium, tail tip, xiphoid process) into euthyroid or hypothyroid adult hosts.
- Administration of propylthiouracil (PTU) to neonatal rats to induce hypothyroidism.
- Assessment of growth and differentiation markers in transplanted tissues and in vivo.
Main Results:
- Hypothyroidism significantly retarded the growth of transplanted endochondral bones (radius, sternum) by day 3 and membranous bones/cartilage (calvarium, tail tip, xiphoid) by day 6.
- Tissue differentiation and epiphyseal ossification were inhibited in hypothyroid hosts.
- Neonatal PTU treatment inhibited tail length and body weight gain.
Conclusions:
- Endochondral bones exhibit TH dependence for growth and differentiation earlier (before postnatal day 4) than membranous bones and cartilage (around the first week).
- TH is essential for normal skeletal development, with distinct temporal requirements for different bone types.
Abstract:
We have studied the development of thyroid hormone dependence for growth and differentiation of rat skeletal tissues. The radius, tail tip or xiphoid process from 1-day-old rats was transplanted in its entirety under the kidney capsule of euthyroid or hypothyroid (TX) adult syngeneic virgin rats and grown there for 3, 6, 9, 12 or 15 days. Pieces of the sternum or calvarium were treated similarly. Growth of transplanted radius and sternum in TX hosts showed significant retardation by day 3, and that of transplanted calvarium, tail tip and xiphoid showed significant inhibition by day 6 post transplantation. Tissue differentiation of all of the transplants was inhibited in TX hosts and the appearance of epiphyseal ossification centers was significantly delayed. Injection of Propylthiouracil (PTU) in solvent into the neonatal rats from day 1 to day 15 post partum inhibited tail length increase by day 7, and body weight gain by day 9, as compared to the growth of solvent injected littermate pups. Our results indicate that the growth and differentiation of endochondral bones are more dependent on TH levels than are those of membranous bones and cartilage. Endochondral bones develop TH dependence for growth and differentiation before day 4 post partum, while the membranous bones and cartilage develop this dependence at the end of the first week.
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