In vivo, human parathyroid hormone fragment (hPTH 1-34) transiently stimulates immediate early response gene expression, but not proliferation, in trabecular bone cells of young rats

J. E. Onyia, Joseph Bidwell, J. Herring, J. Hulman, J. M. Hock

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Intermittent PTH increases trabecular bone mass in vivo by stimulating osteoblast differentiation to increase bone formation. The molecular events that mediate the anabolic effect of PTH on osteoblasts have not been characterized. We investigated if PTH regulated mRNA expression of proto-oncogenes, c-fos, c-jun, and c-myc, early response genes that have been shown to be involved in the regulation of both cell proliferation and differentiation. As PTH also regulates the early expression of the cytokine, interleukin-6 (IL-6), in bone cells in vitro, we also investigated if this occurred in vivo, in concert with the other early response genes. Northern blot hybridization was used to analyze mRNA expression in the metaphysis of the distal femur of young rats. To determine the proliferative state in these femurs, mRNA expression of the cell proliferation marker histone, H4, was assessed. Subcutaneous administration of a single injection of human PTH (1-34) at 8 μg/100 g, a dose known to increase bone forming surfaces, induced rapid and transient expression of c-fos, c-jun, c-myc, and IL-6 mRNA. A second novel transcript for IL-6 was detected, but its significance remains unknown. Induction of all these messages was evident by 1 h; the levels of mRNA returned to baseline after 3-6 h. Concurrently, PTH had a small inhibitory effect on the expression of histone H4 mRNA. We conclude that, in vivo, PTH upregulates cell differentiation in trabecular bone by transient stimulation of the early response genes and IL-6, while downregulating cell proliferation.

Original languageEnglish
Pages (from-to)479-484
Number of pages6
JournalBone
Volume17
Issue number5
DOIs
StatePublished - 1995

Fingerprint

Teriparatide
Immediate-Early Genes
Gene Expression
Messenger RNA
Interleukin-6
Cell Proliferation
Osteoblasts
Histones
Femur
Cell Differentiation
Genes
fos Genes
Anabolic Agents
Bone and Bones
Parathyroid Hormone
Osteogenesis
Northern Blotting
human PTH protein
Cancellous Bone
Up-Regulation

Keywords

  • Bone cell proliferation
  • Bone formation
  • Cytokine IL-6
  • Histone H4
  • hPTH 1-34
  • Immediate early response genes
  • Proto-oncogenes c-fos, c-jun, and c-myc
  • Rats

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Hematology

Cite this

In vivo, human parathyroid hormone fragment (hPTH 1-34) transiently stimulates immediate early response gene expression, but not proliferation, in trabecular bone cells of young rats. / Onyia, J. E.; Bidwell, Joseph; Herring, J.; Hulman, J.; Hock, J. M.

In: Bone, Vol. 17, No. 5, 1995, p. 479-484.

Research output: Contribution to journalArticle

@article{97b7afbf48304d41ab6e402000517128,
title = "In vivo, human parathyroid hormone fragment (hPTH 1-34) transiently stimulates immediate early response gene expression, but not proliferation, in trabecular bone cells of young rats",
abstract = "Intermittent PTH increases trabecular bone mass in vivo by stimulating osteoblast differentiation to increase bone formation. The molecular events that mediate the anabolic effect of PTH on osteoblasts have not been characterized. We investigated if PTH regulated mRNA expression of proto-oncogenes, c-fos, c-jun, and c-myc, early response genes that have been shown to be involved in the regulation of both cell proliferation and differentiation. As PTH also regulates the early expression of the cytokine, interleukin-6 (IL-6), in bone cells in vitro, we also investigated if this occurred in vivo, in concert with the other early response genes. Northern blot hybridization was used to analyze mRNA expression in the metaphysis of the distal femur of young rats. To determine the proliferative state in these femurs, mRNA expression of the cell proliferation marker histone, H4, was assessed. Subcutaneous administration of a single injection of human PTH (1-34) at 8 μg/100 g, a dose known to increase bone forming surfaces, induced rapid and transient expression of c-fos, c-jun, c-myc, and IL-6 mRNA. A second novel transcript for IL-6 was detected, but its significance remains unknown. Induction of all these messages was evident by 1 h; the levels of mRNA returned to baseline after 3-6 h. Concurrently, PTH had a small inhibitory effect on the expression of histone H4 mRNA. We conclude that, in vivo, PTH upregulates cell differentiation in trabecular bone by transient stimulation of the early response genes and IL-6, while downregulating cell proliferation.",
keywords = "Bone cell proliferation, Bone formation, Cytokine IL-6, Histone H4, hPTH 1-34, Immediate early response genes, Proto-oncogenes c-fos, c-jun, and c-myc, Rats",
author = "Onyia, {J. E.} and Joseph Bidwell and J. Herring and J. Hulman and Hock, {J. M.}",
year = "1995",
doi = "10.1016/8756-3282(95)00332-2",
language = "English",
volume = "17",
pages = "479--484",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - In vivo, human parathyroid hormone fragment (hPTH 1-34) transiently stimulates immediate early response gene expression, but not proliferation, in trabecular bone cells of young rats

AU - Onyia, J. E.

AU - Bidwell, Joseph

AU - Herring, J.

AU - Hulman, J.

AU - Hock, J. M.

PY - 1995

Y1 - 1995

N2 - Intermittent PTH increases trabecular bone mass in vivo by stimulating osteoblast differentiation to increase bone formation. The molecular events that mediate the anabolic effect of PTH on osteoblasts have not been characterized. We investigated if PTH regulated mRNA expression of proto-oncogenes, c-fos, c-jun, and c-myc, early response genes that have been shown to be involved in the regulation of both cell proliferation and differentiation. As PTH also regulates the early expression of the cytokine, interleukin-6 (IL-6), in bone cells in vitro, we also investigated if this occurred in vivo, in concert with the other early response genes. Northern blot hybridization was used to analyze mRNA expression in the metaphysis of the distal femur of young rats. To determine the proliferative state in these femurs, mRNA expression of the cell proliferation marker histone, H4, was assessed. Subcutaneous administration of a single injection of human PTH (1-34) at 8 μg/100 g, a dose known to increase bone forming surfaces, induced rapid and transient expression of c-fos, c-jun, c-myc, and IL-6 mRNA. A second novel transcript for IL-6 was detected, but its significance remains unknown. Induction of all these messages was evident by 1 h; the levels of mRNA returned to baseline after 3-6 h. Concurrently, PTH had a small inhibitory effect on the expression of histone H4 mRNA. We conclude that, in vivo, PTH upregulates cell differentiation in trabecular bone by transient stimulation of the early response genes and IL-6, while downregulating cell proliferation.

AB - Intermittent PTH increases trabecular bone mass in vivo by stimulating osteoblast differentiation to increase bone formation. The molecular events that mediate the anabolic effect of PTH on osteoblasts have not been characterized. We investigated if PTH regulated mRNA expression of proto-oncogenes, c-fos, c-jun, and c-myc, early response genes that have been shown to be involved in the regulation of both cell proliferation and differentiation. As PTH also regulates the early expression of the cytokine, interleukin-6 (IL-6), in bone cells in vitro, we also investigated if this occurred in vivo, in concert with the other early response genes. Northern blot hybridization was used to analyze mRNA expression in the metaphysis of the distal femur of young rats. To determine the proliferative state in these femurs, mRNA expression of the cell proliferation marker histone, H4, was assessed. Subcutaneous administration of a single injection of human PTH (1-34) at 8 μg/100 g, a dose known to increase bone forming surfaces, induced rapid and transient expression of c-fos, c-jun, c-myc, and IL-6 mRNA. A second novel transcript for IL-6 was detected, but its significance remains unknown. Induction of all these messages was evident by 1 h; the levels of mRNA returned to baseline after 3-6 h. Concurrently, PTH had a small inhibitory effect on the expression of histone H4 mRNA. We conclude that, in vivo, PTH upregulates cell differentiation in trabecular bone by transient stimulation of the early response genes and IL-6, while downregulating cell proliferation.

KW - Bone cell proliferation

KW - Bone formation

KW - Cytokine IL-6

KW - Histone H4

KW - hPTH 1-34

KW - Immediate early response genes

KW - Proto-oncogenes c-fos, c-jun, and c-myc

KW - Rats

UR - http://www.scopus.com/inward/record.url?scp=0028818206&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028818206&partnerID=8YFLogxK

U2 - 10.1016/8756-3282(95)00332-2

DO - 10.1016/8756-3282(95)00332-2

M3 - Article

C2 - 8579960

AN - SCOPUS:0028818206

VL - 17

SP - 479

EP - 484

JO - Bone

JF - Bone

SN - 8756-3282

IS - 5

ER -