Parathyroid hormone regulation of bone sialoprotein (BSP) gene transcription is mediated through a pituitary-specific transcription factor-1 (Pit-1) motif in the rat BSP gene promoter

Ogata, Yorimasa; Nakao, Sumi; Kim, Richard H.; Li, Jack J.; Furuyama, Shunsuke; Saito, Hiroshi; Sodek, Jaro

doi:10.1016/s0945-053x(00)00085-8

Cited by 60 publications

(50 citation statements)

References 59 publications

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“…tinuous treatment with PTH (1-34), which correlates well to earlier findings demonstrating that PTH effects depend on the in vivo location and differentiation status of the osteoblastic lineage cells (16,25). Furthermore, PTH involvement in osteoblast differentiation is implicated (26).…”

Section: Discussionsupporting

confidence: 86%

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

et al. 2010

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SummaryParathyroid hormone (PTH) strongly stimulates hyaluronan (HA) synthesis and secretion of both normal and carcinogenic cells of the osteoblastic lineage and improves skeletal microarchitecture. HA, a glycosaminoglycan component of the extracellular matrix (ECM), is capable of transmitting ECM-derived signals to regulate cellular function. In this study, we investigated whether the changes of HA metabolism induced by PTH (1-34) and PTH (7-84) peptides in moderately MG-63 and well-differentiated Saos 2 osteosarcoma cell lines, are correlated to their migration capabilities. Our results demonstrate that intermittent PTH (1-34) treatment significantly (P 0.01) supported the migration of MG-63 cells, increased their HA-synthase-2 (HAS2) expression (P 0.001), and enhanced their high-molecular size HA deposition in the pericellular matrix. Both increased endogenous HA production (P 0.01) and treatment with exogenous high-molecular weight HA (P 0.05) correlated to a significant increase of MG-63 cell migration capacity. Transfection with siHAS2 showed that PTH (1-34), mainly through HAS2, enhanced HA and regulated MG-63 cell motility. Interestingly, continuous PTH (1-34) treatment stimulated both Saos 2 cell HAS2 (P 0.001) and HAS1 (P 0.001) isoform expression inhibited their HYAL2 expression (P 0.001) and modestly (P 0.05) enhanced their migration. Therefore, the PTH (1-34) administration mode appears to distinctly modulate the migratory responses of the MG-63 moderately and Saos 2 well-differentiated osteosarcoma cell lines. Conclusively, the obtained data suggest that there is a regulatory effect of PTH (1-34), in an administration mode-dependent manner, on HA metabolism that is essential for osteosarcoma cell migration.

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Section: Discussionsupporting

confidence: 86%

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

et al. 2010

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“…Sodium orthovanadate (50 M) and okadaic acid (50 nM) were used for tyrosine phosphatase and serine-threonine phosphatase inhibition, respectively (53,54). Forskolin (1 M) was used for activation of adenylate cyclase (45). Oligonucleotide-directed mutagenesis by PCR was utilized to introduce dinucleotide substitutions using the QuikChange site-directed mutagenesis kit (Stratagene).…”

Section: Experimrntal Proceduresmentioning

confidence: 99%

“…These promoters include a functional inverted TATA element (nt Ϫ24 to Ϫ19) (38), which overlaps a vitamin D response element (39), and an inverted CCAAT box (Ϫ50 to Ϫ46), which is required for basal transcription (40,41). In addition, a fibroblast growth factor 2 (FGF2) response element (FRE; Ϫ92 to Ϫ85) (42), a cAMP response element (CRE; Ϫ75 to Ϫ68) (43), a transforming growth factor-␤ activation element (Ϫ499 to Ϫ485) (44), a pituitary-specific transcription factor-1 (Pit-1) motif (Ϫ111 to Ϫ105) that mediates the stimulatory effects of parathyroid hormone (45), and a homeodomain binding element (Ϫ199 to Ϫ192) (46) have been characterized. Further upstream, a glucocorticoid response element overlapping an AP-1 site (27,47) has also been identified.…”

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confidence: 99%

Prostaglandin E2 Stimulates Bone Sialoprotein (BSP) Expression through cAMP and Fibroblast Growth Factor 2 Response Elements in the Proximal Promoter of the Rat BSP Gene

Samoto

Shimizu

Matsuda-Honjyo

et al. 2003

Journal of Biological Chemistry

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Bone sialoprotein (BSP), an early marker of osteoblast differentiation, has been implicated in the nucleation of hydroxyapatite during de novo bone formation. Prostaglandin E 2 (PGE 2 ) has anabolic effects on proliferation and differentiation of osteoblasts via diverse signal transduction systems. Because PGE 2 increases the proportion of functional osteoblasts in fetal rat calvarial cell cultures, we investigated the regulation of BSP, as an osteoblastic marker, by PGE 2 . Treatment of rat osteosarcoma UMR 106 cells with 3 M, 300 nM, and 30 nM PGE 2 increased the steady state levels of BSP mRNA about 2.7-, 2.5-, and 2.4-fold after 12 h. From transient transfection assays, the constructs including the promoter sequence of nucleotides (nt) ؊116 to ؉60 (pLUC3) were found to enhance transcriptional activity 3.8-and 2.2-fold treated with 3 M and 30 nM PGE 2 for 12 h. 2-bp mutations were made in an inverted CCAAT box (between nt ؊50 and ؊46), a cAMP response element (CRE; between nt ؊75 and ؊68), a fibroblast growth factor 2 response element (FRE; nt ؊92 to ؊85), and a pituitaryspecific transcription factor-1 motif (between nt ؊111 and ؊105) within pLUC3 and pLUC7 constructs. Transcriptional stimulation by PGE 2 was almost completed abrogated in constructs that included 2-bp mutations in either the CRE and FRE. In gel shift analyses an increased binding of nuclear extract components to double-stranded oligonucleotide probes containing CRE and FRE was observed following treatment with PGE 2 . These studies show that PGE 2 induces BSP transcription in UMR 106 cells through juxtaposed CRE and FRE elements in the proximal promoter of the BSP gene.Prostaglandins are considered important local factors that modulate bone metabolism through their effects on osteoblastic cells and osteoclasts (1, 2). Prostaglandin E 2 (PGE 2 ), 1 a major eicosanoid produced by osteoblasts, is a potent stimulator of bone resorption (3) that can stimulate the formation of osteoclast-like multinuclear cells in mouse bone marrow cultures (4, 5). The effects of PGE 2 on osteoclastogenesis are, at least in part, mediated by osteogenic cells, which express macrophage colony-stimulating factor (6) and receptor activator of nuclear factor B ligand (RANKL) (7) that promote, and osteoprotegerin, a decoy receptor for RANKL (8), that suppresses osteoclast formation. PGE 2 has been shown to stimulate RANKL and inhibit osteoprotegerin production (7, 9) and also increases production of interleukin-6, which can further enhance osteoclastogenesis (10 -12). In contrast, studies have revealed that PGE 2 also has bone-forming activity (2, 13). Treatment of male, female, and overiectomized mice with PGE 2 increases bone mass in vivo (14), whereas PGE 2 stimulates collagen and DNA synthesis and induces bone growth in calvarial organ (15) and cell cultures in vitro (16, 17). However, PGE 2 can either stimulate or inhibit cellular growth and differentiation of osteoblastic cells depending on PGE 2 concentration (15,18,19).To explain the diverse effects of PGE 2 , th...

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“…The ability of PTH to regulate gene expression is dependent on the activation of specific transcription factors such as cAMPresponse element-binding protein (CREB) (36, 37), AP-1 family members (38,39), pituitary-specific transcription factor 1 (40), and RUNX2 (38). Although it is well known that PTH induces OCN gene expression, the mechanism mediating this regulation is not known.…”

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confidence: 99%

Parathyroid Hormone Induction of the Osteocalcin Gene

Jiang

Franceschi

Boules

et al. 2004

Journal of Biological Chemistry

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Parathyroid hormone (PTH) is an important peptide hormone regulator of bone formation and osteoblast activity. However, its mechanism of action in bone cells is largely unknown. This study examined the effect of PTH on mouse osteocalcin gene expression in MC3T3-E1 preosteoblastic cells and primary cultures of bone marrow stromal cells. PTH increased the levels of osteocalcin mRNA 4 -5-fold in both cell types. PTH also stimulated transcriptional activity of a 1.3-kb fragment of the mouse osteocalcin gene 2 (mOG2) promoter. Inhibitor studies revealed a requirement for protein kinase A, protein kinase C, and mitogen-activated protein kinase pathways in the PTH response. Deletion of the mOG2 promoter sequence from ؊1316 to ؊116 caused no loss in PTH responsiveness whereas deletion from ؊116 to ؊34 completely prevented PTH stimulation. Interestingly, this promoter region does not contain the RUNX2 binding site shown to be necessary for PTH responsiveness in other systems. Nuclear extracts from PTH-treated MC3T3-E1 cells exhibited increased binding to OSE1, a previously described osteoblast-specific enhancer in the mOG2 promoter. Furthermore, mutation of OSE1 in DNA transfection assays established the requirement for this element in the PTH response. Collectively, these studies establish that actions of PTH on the osteocalcin gene are mediated by multiple signaling pathways and require OSE1 and associated nuclear proteins.Parathyroid hormone (PTH) 1 is a major regulator of calcium homeostasis. PTH has catabolic and anabolic effects on osteoblasts and bone in vitro and in vivo, which depend on the temporal pattern of administration; continuous administration decreases bone mass whereas intermittent administration increases bone mass (1-4). PTH functions through the PTH-1 receptor, a G protein-coupled receptor that is expressed in osteoblasts (5-7). Binding of PTH to its receptor activates multiple intracellular signaling pathways that involve cyclic cAMP, inositol phosphates, intracellular Ca 2ϩ , protein kinases A and C (2), and the extracellular signal-regulated kinase/ mitogen-activated protein kinase (MAPK) pathway (8, 9).Osteocalcin (OCN), a 5700-dalton ␥-carboxyglutamic acidcontaining noncollagenous protein, is a major component of the bone extracellular matrix. Although the functions of OCN are poorly understood, gene deletion studies suggest possible functions in bone remodeling (10). The expression of OCN is regulated by a number of calcitropic hormones and growth factors including 1,25-dihydroxy vitamin D 3 (11-13), glucocorticoids (14, 15), PTH (16), bone morphogenetic proteins (17), basic fibroblast growth factor 2 (18), tumor necrosis factor-␣ (19), and transforming growth factor ␤ (20). A number of transcription factors that bind to specific regions of the osteocalcin gene promoter have also been identified. These factors include AP-1 family members (21, 22), MSX-2/HOX 8.1 (23, 24), DLX-5 (25), CCAAT/enhancer binding proteins (26), and RUNX2 (27), the osteoblast-specific product of the Cbfa1 gene. These f...

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Parathyroid hormone regulation of bone sialoprotein (BSP) gene transcription is mediated through a pituitary-specific transcription factor-1 (Pit-1) motif in the rat BSP gene promoter

Cited by 60 publications

References 59 publications

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

Prostaglandin E2 Stimulates Bone Sialoprotein (BSP) Expression through cAMP and Fibroblast Growth Factor 2 Response Elements in the Proximal Promoter of the Rat BSP Gene

Parathyroid Hormone Induction of the Osteocalcin Gene

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