Loss of the transcription factor p45 NF-E2 results in a developmental arrest of megakaryocyte differentiation and the onset of a high bone mass phenotype

Melissa Kacena, C. M. Gundberg, T. Nelson, M. C. Horowitz

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

NF-E2 is a transcription factor required for megakaryocyte differentiation. The phenotype of mice deficient in p45 NF-E2 has been characterized by increased numbers of immature megakaryocytes and the absence of functional platelets. These mice also exhibited a high bone mass phenotype with up to a 6-fold increase in trabecular bone volume and a 3- to 5-fold increase in the bone formation rate. Our data indicated that both osteoblast and osteoclast numbers were increased in vivo with a 4- to 10-fold increase in osteoblast number/tissue area and approximately a 5-fold increase in osteoclast number/tissue area. Serum osteocalcin levels were also increased in NF-E2-deficient mice, corroborating the histomorphometric data and confirming that the osteoblasts were functional. Urinary cross-links levels were measured to confirm osteoclast activity. Interestingly, the increased bone was observed only in bony sites of hematopoiesis, and was not seen in flat bones such as calvariae. We showed that cells of the osteoblast lineage do not express NF-E2 mRNA. The increased bone phenotype was adoptively transferred into irradiated wild-type mice using spleen cells from NF-E2-deficient mice. These observations suggest that a megakaryocyte-osteoblast interaction occurs which is anabolic for bone.

Original languageEnglish (US)
Pages (from-to)215-223
Number of pages9
JournalBone
Volume36
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

Fingerprint

NF-E2 Transcription Factor
Megakaryocytes
Osteoblasts
Bone and Bones
Osteoclasts
Phenotype
Osteocalcin
Hematopoiesis
Cell Lineage
Osteogenesis
Skull
Transcription Factors
Blood Platelets
Spleen
MASS syndrome
Messenger RNA
Serum

Keywords

  • Anabolic
  • Megakaryocytes
  • Osteoblasts
  • p45 NF-E2
  • Transcription factors

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Loss of the transcription factor p45 NF-E2 results in a developmental arrest of megakaryocyte differentiation and the onset of a high bone mass phenotype. / Kacena, Melissa; Gundberg, C. M.; Nelson, T.; Horowitz, M. C.

In: Bone, Vol. 36, No. 2, 02.2005, p. 215-223.

Research output: Contribution to journalArticle

@article{c02b62b4a9154df891f187a5a7d296a4,
title = "Loss of the transcription factor p45 NF-E2 results in a developmental arrest of megakaryocyte differentiation and the onset of a high bone mass phenotype",
abstract = "NF-E2 is a transcription factor required for megakaryocyte differentiation. The phenotype of mice deficient in p45 NF-E2 has been characterized by increased numbers of immature megakaryocytes and the absence of functional platelets. These mice also exhibited a high bone mass phenotype with up to a 6-fold increase in trabecular bone volume and a 3- to 5-fold increase in the bone formation rate. Our data indicated that both osteoblast and osteoclast numbers were increased in vivo with a 4- to 10-fold increase in osteoblast number/tissue area and approximately a 5-fold increase in osteoclast number/tissue area. Serum osteocalcin levels were also increased in NF-E2-deficient mice, corroborating the histomorphometric data and confirming that the osteoblasts were functional. Urinary cross-links levels were measured to confirm osteoclast activity. Interestingly, the increased bone was observed only in bony sites of hematopoiesis, and was not seen in flat bones such as calvariae. We showed that cells of the osteoblast lineage do not express NF-E2 mRNA. The increased bone phenotype was adoptively transferred into irradiated wild-type mice using spleen cells from NF-E2-deficient mice. These observations suggest that a megakaryocyte-osteoblast interaction occurs which is anabolic for bone.",
keywords = "Anabolic, Megakaryocytes, Osteoblasts, p45 NF-E2, Transcription factors",
author = "Melissa Kacena and Gundberg, {C. M.} and T. Nelson and Horowitz, {M. C.}",
year = "2005",
month = "2",
doi = "10.1016/j.bone.2004.09.024",
language = "English (US)",
volume = "36",
pages = "215--223",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Loss of the transcription factor p45 NF-E2 results in a developmental arrest of megakaryocyte differentiation and the onset of a high bone mass phenotype

AU - Kacena, Melissa

AU - Gundberg, C. M.

AU - Nelson, T.

AU - Horowitz, M. C.

PY - 2005/2

Y1 - 2005/2

N2 - NF-E2 is a transcription factor required for megakaryocyte differentiation. The phenotype of mice deficient in p45 NF-E2 has been characterized by increased numbers of immature megakaryocytes and the absence of functional platelets. These mice also exhibited a high bone mass phenotype with up to a 6-fold increase in trabecular bone volume and a 3- to 5-fold increase in the bone formation rate. Our data indicated that both osteoblast and osteoclast numbers were increased in vivo with a 4- to 10-fold increase in osteoblast number/tissue area and approximately a 5-fold increase in osteoclast number/tissue area. Serum osteocalcin levels were also increased in NF-E2-deficient mice, corroborating the histomorphometric data and confirming that the osteoblasts were functional. Urinary cross-links levels were measured to confirm osteoclast activity. Interestingly, the increased bone was observed only in bony sites of hematopoiesis, and was not seen in flat bones such as calvariae. We showed that cells of the osteoblast lineage do not express NF-E2 mRNA. The increased bone phenotype was adoptively transferred into irradiated wild-type mice using spleen cells from NF-E2-deficient mice. These observations suggest that a megakaryocyte-osteoblast interaction occurs which is anabolic for bone.

AB - NF-E2 is a transcription factor required for megakaryocyte differentiation. The phenotype of mice deficient in p45 NF-E2 has been characterized by increased numbers of immature megakaryocytes and the absence of functional platelets. These mice also exhibited a high bone mass phenotype with up to a 6-fold increase in trabecular bone volume and a 3- to 5-fold increase in the bone formation rate. Our data indicated that both osteoblast and osteoclast numbers were increased in vivo with a 4- to 10-fold increase in osteoblast number/tissue area and approximately a 5-fold increase in osteoclast number/tissue area. Serum osteocalcin levels were also increased in NF-E2-deficient mice, corroborating the histomorphometric data and confirming that the osteoblasts were functional. Urinary cross-links levels were measured to confirm osteoclast activity. Interestingly, the increased bone was observed only in bony sites of hematopoiesis, and was not seen in flat bones such as calvariae. We showed that cells of the osteoblast lineage do not express NF-E2 mRNA. The increased bone phenotype was adoptively transferred into irradiated wild-type mice using spleen cells from NF-E2-deficient mice. These observations suggest that a megakaryocyte-osteoblast interaction occurs which is anabolic for bone.

KW - Anabolic

KW - Megakaryocytes

KW - Osteoblasts

KW - p45 NF-E2

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=14144251106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14144251106&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2004.09.024

DO - 10.1016/j.bone.2004.09.024

M3 - Article

VL - 36

SP - 215

EP - 223

JO - Bone

JF - Bone

SN - 8756-3282

IS - 2

ER -