Mechanism of Thyroid Hormone-Induced Osteoporosis
Abstract
The goal of the research is to determine the cause of the osteoporosis resulting from excessive thyroid hormone. The question is complex, due to the fact that thyroid- hormone is also critical for bone growth. Based upon our previous findings that thyroid hormone increased the production of both the osteoclastogenic cytokine interleukin-6 and the important bone growth factor, insulin-like growth factor (IGF-I), we proposed to determine the roles of these local factors in the effects of thyroid hormone to stimulate both bone growth and bone loss. Also we proposed to determine the pathways by which thyroid hormone increases these local factors in bone. During the second year of the grant we have completed studies that demonstrate that IGF-I mediates anabolic effects of T3 on proline incorporation, alkaline phosphatase and osteocalcin. The decline in IGF-I production that we previously observed at pathophysiologic T3 concentrations could thus represent part of the mechanism for the bone loss. We are continuing studies on the role of IL-6 with the establishment of a model for testing effects on differentiation. Several new strategies for examining T3 effects on IGF-I and IL-6 gene expression, including the molecular reconstruction of the pathway in non-osteoblastic cells are being pursued.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA368354
Entities
People
- Paula H. Stern
Organizations
- Northwestern University