TY - JOUR
T1 - TIEG1 null mouse-derived osteoblasts are defective in mineralization and in support of osteoclast differentiation in vitro
AU - Subramaniam, Malayannan
AU - Gorny, Genevieve
AU - Johnsen, Steven A.
AU - Monroe, David G.
AU - Evans, Glenda L.
AU - Fraser, Daniel G.
AU - Rickard, David J.
AU - Rasmussen, Kay
AU - Van Deursen, Jan M.A.
AU - Turner, Russell T.
AU - Oursler, Merry Jo
AU - Spelsberg, Thomas C.
PY - 2005/2
Y1 - 2005/2
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.25.3.1191-1199.2005
DO - 10.1128/MCB.25.3.1191-1199.2005
M3 - Article
C2 - 15657444
AN - SCOPUS:19944433990
SN - 0270-7306
VL - 25
SP - 1191
EP - 1199
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 3
ER -