TY - JOUR
T1 - Amphiregulin is a novel growth factor involved in normal bone development and in the cellular response to parathyroid hormone stimulation
AU - Qin, Ling
AU - Tamasi, Joseph
AU - Raggatt, Liza
AU - Li, Xin
AU - Feyen, Jean H M
AU - Lee, David C.
AU - DiCicco-Bloom, Emanuel
AU - Partridge, Nicola C.
PY - 2005/2/4
Y1 - 2005/2/4
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M409807200
DO - 10.1074/jbc.M409807200
M3 - Article
C2 - 15509566
AN - SCOPUS:13544265673
SN - 0021-9258
VL - 280
SP - 3974
EP - 3981
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -