Autor: |
Subramaniam, Malayannan, Gorny, Genevieve, Johnsen, Steven A., Monroe, David G., Evans, Glenda L., Fraser, Daniel G., Rickard, David J., Rasmussen, Kay, Van Deursen, Jan M. A., Turner, Russell T., Oursler, Merry Jo, Spelsberg, Thomas C. |
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Zdroj: |
Molecular & Cellular Biology; Feb2005, Vol. 25 Issue 3, p1191-1199, 9p |
Abstrakt: |
Transforming growth factor β-inducible early gene 1 (TIEG1) is a member of the Krüppel-like transcription factor family. To understand the physiological role of TIEG1, we generated TIEG-/- (null) mice and found that the TIEG-/- mice had increased osteoblast numbers with no increased bone formation parameters. However, when calvarial osteoblasts (OBs) were isolated from neonatal TIEG-/- and TIEG+/+ mice and cultured in vitro, the TIEG-/- cells displayed reduced expression of important OB differentiation markers. When the OBs were differentiated in vitro by treatment with bone morphogenic protein 2, the OBs from TIEG+/+ calvaria displayed several mineralized nodules in culture, whereas those from TIEG-/- mice showed no nodules. To characterize the OBs' ability to support osteoclast differentiation, the OBs from TIEG+/+ and TIEG-/- mice were cultured with marrow and spleen cells from TIEG+/+ mice. Significantly fewer osteoclasts developed when TIEG-/- OBs were used to support osteoclast differentiation than when TIEG+/+ OBs were used. Examination of gene expression in the TIEG-/- OBs revealed decreased RANKL and increased OPG expression compared to TIEG+/+ OBs. The addition of RANKL to these cocultures only partially restored the ability of TIEG-/- OBs to support osteoclast differentiation, whereas M-CSF alone or combined with RANKL had no additional effect on osteoclast differentiation. We conclude from these data that TIEG1 expression in OBs is critical for both osteoblast-mediated mineralization and osteoblast support of osteoclast differentiation. [ABSTRACT FROM AUTHOR] |
Databáze: |
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