Parathyroid hormone stimulation and PKA signaling of latent transforming growth factor-beta binding protein-1 (LTBP-1) mRNA expression in osteoblastic cells.

Parathyroid hormone (PTH) regulates bone remodeling and calcium homeostasis by acting on osteoblasts. Recently, the gene expression profile changes in the rat PTH (1-34, 10(-8)M)-treated rat osteoblastic osteosarcoma cell line, UMR 106-01, using DNA microarray analysis showed that mRNA for LTBP-1, a latent transforming growth factor (TGF-beta)-binding protein is stimulated by PTH. Latent TGF-beta binding proteins (LTBPs) are required for the proper folding and secretion of TGF-beta, thus modifying the activity of TGF-beta, which is a local factor necessary for bone remodeling. We show here by real time RT-PCR that PTH-stimulated LTBP-1 mRNA expression in rat and mouse preosteoblastic cells. PTH also stimulated LTBP-1 mRNA expression in all stages of rat primary osteoblastic cells but extended expression was found in differentiating osteoblasts. PTH also stimulated TGF-beta1 mRNA expression in rat primary osteoblastic cells, indicating a link between systemic and local factors for intracellular signaling in osteoblasts. An additive effect on LTBP-1 mRNA expression was found when UMR 106-01 cells were treated with PTH and TGF-beta1 together. We further examined the signaling pathways responsible for PTH-stimulated LTBP-1 and TGF-beta1 mRNA expression in UMR 106-01 cells. The PTH stimulation of LTBP-1 and TGF-beta1 mRNA expression was dependent on the PKA and the MAPK (MEK and p38 MAPK) pathways, respectively in these cells, suggesting that PTH mediates its effects on osteoblasts by several intracellular signaling pathways. Overall, we demonstrate here that PTH stimulates LTBP-1 mRNA expression in osteoblastic cells and this is PKA-dependent. This event may be important for PTH action via TGF-beta in bone remodeling.

Kwok S ，Qin L ，Partridge NC ，Selvamurugan N ... -  《JOURNAL OF CELLULAR BIOCHEMISTRY》

Expression and release of the latent transforming growth factor beta binding protein by hepatocytes from rat liver.

Roth S ，Schurek J ，Gressner AM 《HEPATOLOGY》

Expression and matrix deposition of latent transforming growth factor beta binding proteins in normal and fibrotic rat liver and transdifferentiating hepatic stellate cells in culture.

Breitkopf K ，Lahme B ，Tag CG ，Gressner AM ... -  《HEPATOLOGY》

Induction of human LTBP-3 promoter activity by TGF-beta1 is mediated by Smad3/4 and AP-1 binding elements.

Kantola AK ，Keski-Oja J ，Koli K 《GENE》

Parathyroid hormone enhances bone morphogenetic protein activity by increasing intracellular 3', 5'-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-E1 cells.

Nakao Y ，Koike T ，Ohta Y ，Manaka T ，Imai Y ，Takaoka K ... -  《-》