PMID:15657444

Citation	Subramaniam, M, Gorny, G, Johnsen, SA, Monroe, DG, Evans, GL, Fraser, DG, Rickard, DJ, Rasmussen, K, van Deursen, JM, Turner, RT, Oursler, MJ and Spelsberg, TC (2005) TIEG1 null mouse-derived osteoblasts are defective in mineralization and in support of osteoclast differentiation in vitro. Mol. Cell. Biol. 25:1191-9
Abstract	Transforming growth factor beta-inducible early gene 1 (TIEG1) is a member of the Kruppel-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.
Links	PubMed PMC543998 Online version:10.1128/MCB.25.3.1191-1199.2005
Keywords	Animals; Bone Marrow/metabolism; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins/metabolism; Calcification, Physiologic/physiology; Carrier Proteins/metabolism; Cell Differentiation/physiology; Cell Proliferation; Coculture Techniques; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Glycoproteins/metabolism; Membrane Glycoproteins/metabolism; Mice; Mice, Knockout; Osteoblasts/cytology; Osteoblasts/metabolism; Osteoclasts/cytology; Osteoclasts/metabolism; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear/metabolism; Receptors, Tumor Necrosis Factor; Spleen/cytology; Spleen/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transforming Growth Factor beta/metabolism
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