Amphiregulin is a novel growth factor involved in normal bone development and in the cellular response to parathyroid hormone stimulation

Ling Qin, Joseph Tamasi, Liza Raggatt, Xin Li, Jean H M Feyen, David C. Lee, Emanuel DiCicco-Bloom, Nicola C. Partridge

Research output: Contribution to journalArticle

Abstract

Parathyroid hormone (PTH) is the major mediator of calcium homeostasis and bone remodeling and is now known to be an effective drug for osteoporosis treatment. Yet the mechanisms responsible for its functions in bone are largely unknown. Here we report that the expression of amphiregulin (AR), a member of the epidermal growth factor (EGF) family, is rapidly and highly up-regulated by PTH in several osteoblastic cell lines and bone tissues. Other osteotropic hormones (1α,25-dihydroxyvitamin D3 and prostaglandin E 2) also strongly stimulate AR expression. We found all EGF-like ligands and their receptors are expressed in osteoblasts, but AR is the only member that is highly regulated by PTH. Functional studies demonstrated that although AR is a potent growth factor for preosteoblasts, it completely inhibits further differentiation. AR also strongly and quickly stimulated Akt and ERK phosphorylation and c-fos and c-jun expression in an EGF receptor-dependent manner. Moreover, AR null mice displayed significantly less tibial trabecular bone than wild-type mice. Taken together, we have identified a novel growth factor that is PTH-regulated and appears to have an important role in bone metabolism.

Original languageEnglish (US)
Pages (from-to)3974-3981
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number5
DOIs
StatePublished - Feb 4 2005

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Bone Development
Parathyroid Hormone
Intercellular Signaling Peptides and Proteins
Bone
Epidermal Growth Factor
Bone and Bones
Phosphorylation
Calcitriol
Bone Remodeling
Osteoblasts
Prostaglandins E
Epidermal Growth Factor Receptor
Metabolism
Osteoporosis
Amphiregulin
Homeostasis
Cells
Hormones
Tissue
Ligands

ASJC Scopus subject areas

  • Biochemistry

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Amphiregulin is a novel growth factor involved in normal bone development and in the cellular response to parathyroid hormone stimulation. / Qin, Ling; Tamasi, Joseph; Raggatt, Liza; Li, Xin; Feyen, Jean H M; Lee, David C.; DiCicco-Bloom, Emanuel; Partridge, Nicola C.

In: Journal of Biological Chemistry, Vol. 280, No. 5, 04.02.2005, p. 3974-3981.

Research output: Contribution to journalArticle

Qin, Ling ; Tamasi, Joseph ; Raggatt, Liza ; Li, Xin ; Feyen, Jean H M ; Lee, David C. ; DiCicco-Bloom, Emanuel ; Partridge, Nicola C. / Amphiregulin is a novel growth factor involved in normal bone development and in the cellular response to parathyroid hormone stimulation. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 5. pp. 3974-3981.
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