TIEG1 null mouse-derived osteoblasts are defective in mineralization and in support of osteoclast differentiation in vitro

Malayannan Subramaniam, Genevieve Gorny, Steven A. Johnsen, David G. Monroe, Glenda L. Evans, Daniel G. Fraser, David J. Rickard, Kay Rasmussen, Jan M.A. Van Deursen, Russell T. Turner, Merry Jo Oursler, Thomas C. Spelsberg

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1191-1199
Number of pages9
JournalMolecular and cellular biology
Volume25
Issue number3
DOIs
StatePublished - Feb 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'TIEG1 null mouse-derived osteoblasts are defective in mineralization and in support of osteoclast differentiation in vitro'. Together they form a unique fingerprint.

  • Cite this