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Thyroid Hormone Excess Increases Insulin-Like Growth Factor I Transcripts in Bone Marrow Cell Cultures: Divergent Effects on Vertebral and Femoral Cell Cultures¹

Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical Center, Worcester, Massachusetts 01655

Address all correspondence and requests for reprints to: Dr. Moira Milne, Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts 01655.

Thyroid hormones (T₃ and T₄) regulate bone development, growth, and turnover. Studies have suggested that different skeletal sites respond differently to thyroid hormones. Therefore, we examined the in vitro T₃ responsiveness of cells committed to the osteoblast lineage as a function of skeletal location. Bone marrow cells derived from female rat femurs and vertebrae were cultured using conditions that induce osteogenic differentiation. Cells from both sites formed mineralized bone nodules in primary and secondary culture. In femoral cultures, collagen type I (coll I) and osteocalcin (OC) messenger RNA (mRNA) levels increased from the earliest time point examined (day 3) to a maximum on day 12 and thereafter declined to undetectable levels. T₃ increased both OC and coll I mRNA, resulting in a continuous expression throughout the culture period. Insulin-like growth factor I (IGF-I) gene expression was detected at very low levels by Northern analysis of femoral total RNA, and T₃ only marginally enhanced IGF-I mRNA levels. In vertebral cultures, OC and coll I mRNA levels also increased with time in culture, but remained expressed throughout the culture period. OC and coll I mRNA levels were not markedly altered in response to T₃. In contrast to femoral cells, IGF-I gene expression was easily visualized in Northern blots from untreated vertebral cultures and was markedly increased by the addition of T₃. The continuous presence of T₃ (10^-7 M) in the medium for 18 days caused a marked decrease in the number of alkaline phosphatase-positive colonies formed in femoral secondary cultures, but only a slight decrease in the number in vertebral cultures. In addition, short term (6 days) exposure to T₃ (10^-7 M) at the beginning of the culture period decreased alkaline phosphatase activity in femoral cultures, but not in vertebral cultures. These findings indicate that there are skeletal site-dependent differences in the in vitro responses of cells of the osteoblastic lineage to thyroid hormone.

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