Parathyroid hormone (1-34) augments angiopoietin-1 expression in human osteoblast-like cells.
Parathyroid hormone (PTH) is a major regulatory factor in skeletal physiology. However, the molecular mechanism underlying the effects of PTH on bones has yet to be elucidated in detail. Recently, some reports have demonstrated the crucial role of bone vasculature with regard to bone density. Angiopoietin-1 (Ang-1), along with VEGF, has been established as a primary angiogenic regulatory agent. In this study, we have attempted to characterize the effects of PTH (1-34) on Ang-1 expression and signaling molecules, employing primary-cultured human osteoblast-like cells. Quiescent osteoblasts were exposed to PTH (1-34), after which Ang-1 expression was determined at the mRNA and protein levels. Reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated that Ang-1 mRNA expression increased as the result of PTH (1-34) treatment. The expression of the Ang-1 protein was also augmented as the result of treatment with PTH (1-34). An adenylyl cyclase activator, forskolin, was shown to induce Ang-1 mRNA expression, whereas the protein kinase A inhibitor, H-89, blocked the PTH (1-34)-mediated expression of Ang-1 mRNA. These findings indicate that PTH (1-34)-mediated Ang-1 expression involves adenylyl cyclase-protein kinase A dependent signaling. Our observations also show that Ang-1 may perform a crucial role in the effects of PTH (1-34) on bones, possibly involving alterations in bone vasculature.
Park
J H
JH
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea. parkjh@chonbuk.ac.kr
Song
H I
HI
Rho
J M
JM
Kim
M R
MR
Kim
J R
JR
Park
B H
BH
Park
T S
TS
Baek
H S
HS
D042683:Angiopoietin-1 / Q000235:genetics*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects
D042683:Angiopoietin-1; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D012333:RNA, Messenger; D005576:Colforsin