Parathyroid hormone alters collagen synthesis and procollagen mRNA levels in fetal rat calvaria.

Kream, Barbara E.; Rowe, David W.; Gworek, Susan C.; Raisz, Lawrence G.

doi:10.1073/pnas.77.10.5654

Cited by 118 publications

(41 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both positive and negative regulation has been shown to take place depending on the inducer (1 1,[13][14][15][16][17][18][19][20][21][22][23][24]. For example, cortisol and other antiinflammatory steroids, parpthyroid hormone, and y-interferon all cause a specific decrease in the cellular concentration of translatable type I procollagen mRNA (16, 18, genes with a consequent decrease in the levels of type I procollagen mRNAs (20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts.

Raghow¹,

Postlethwaite²,

Keski‐Oja³

et al. 1987

J. Clin. Invest.

453

212

View full text Add to dashboard Cite

Transforming growth factor-jB (TGF,8), when injected subcutaneously into newborn mice, induces a rapid fibrotic response, stimulates chemotaxis, and elevates the rates of biosynthesis of collagen and fibronectin by fibroblasts in vitro. We explored the molecular mechanisms of TGFft-mediated stimulation of collagen and fibronectin synthesis in cultured human foreskin fibroblasts.TGF,/ preferentially stimulated the synthesis of fibronectin and type I procollagen chains 3-5-fold as shown by polypeptide analysis. Concomitant elevation in the steady state levels of messenger RNAs (mRNAs) coding for type I procollagen and fibronectin also occurred but without a net increase in the rate of transcription of either of these genes. The preferential stabilization of mRNAs specifying type I procollagen and fibronectin provides a partial explanation for the mechanisms by which TGFft enhances the synthesis of type I procollagen and fibronectin in mesenchymal cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts.

Raghow¹,

Postlethwaite²,

Keski‐Oja³

et al. 1987

J. Clin. Invest.

453

212

View full text Add to dashboard Cite

show abstract

“…(ii) In c-fos Ϫ/Ϫ mouse osteoblasts, basal and PTH induction of collagenase-3 transcripts was significantly reduced. 2 (iii) Whether CREB or ATF-1 binds to the AP-1 site in a gel shift, this protein was not phosphorylated in response to PTH, since anti-phospho-CREB antibody did not cause a supershift (Fig. 7), whereas we know this antibody will supershift PTH-induced phosphorylated CREB bound to a cyclic AMP-response element in the c-fos gene (24).…”

Section: Figmentioning

confidence: 99%

Parathyroid Hormone Regulates the Rat Collagenase-3 Promoter in Osteoblastic Cells through the Cooperative Interaction of the Activator Protein-1 Site and the runt Domain Binding Sequence

Selvamurugan

Chou

Pearman

et al. 1998

Journal of Biological Chemistry

165

181

View full text Add to dashboard Cite

Parathyroid hormone induces collagenase-3 gene transcription in rat osteoblastic cells. Here, we characterized the basal, parathyroid hormone regulatory regions of the rat collagenase-3 gene and the proteins involved in this regulation. The minimal parathyroid hormone-responsive region was observed to be between base pairs ؊38 and ؊148. Deleted and mutated constructs showed that the activator protein-1 and the runt domain binding sites are both required for basal expression and parathyroid hormone activation of this gene. The runt domain site is identical to an osteoblast-specific element-2 or acute myelogenous leukemia binding sequence in the mouse and rat osteocalcin genes, respectively. Overexpression of an acute myelogenous leukemia-1 repressor protein inhibited parathyroid hormone activation of the promoter, indicating a requirement of acute myelogenous leukemiarelated factor(s) for this activity. Overexpression of c-Fos, c-Jun, osteoblast-specific factor-2, and core binding factor-␤ increased the response to parathyroid hormone of the wild type (؊148) promoter but not with mutation of either or both the activator protein-1 and runt domain binding sites. In summary, we conclude that there is a cooperative interaction of acute myelogenous leukemia/ polyomavirus enhancer-binding protein-2-related factor(s) binding to the runt domain binding site with members of the activator protein-1 transcription factor family binding to the activator protein-1 site in the rat collagenase-3 gene in response to parathyroid hormone in osteoblastic cells. Parathyroid hormone (PTH)1 is an essential regulator of calcium homeostasis (1). In addition to kidney, its major target tissue is bone, the body's main calcium store. While PTH increases serum calcium partly by activating osteoclasts, these cells do not display PTH receptors. Instead, PTH exerts a direct effect on osteoblasts, causing them to cease synthesis of type I collagen (2, 3), the major organic component of bone. Most relevant to the current study, we and others have demonstrated that, in vitro, PTH can stimulate the osteoblastic synthesis of interstitial collagenase, the enzyme that specifically degrades fibrillar collagens (4, 5). Although collagenase synthesis and secretion by osteoblasts has been well documented, the signaling mechanism through which PTH stimulates its expression in this cell type is not fully understood. We have employed the UMR 106-01 (UMR) rat osteosarcoma cell line to investigate PTH regulation of collagenase-3 gene expression in osteoblasts. This cell line displays classical osteoblastic markers including PTH receptors, type I collagen, and high alkaline phosphatase expression. Most importantly to the present study, UMR cells decrease collagen synthesis and begin production of interstitial collagenase in response to PTH treatment. Previously, we reported that UMR cell collagenase induction by PTH is due to an increase in transcription and is a secondary response since it requires de novo protein synthesis (6). In the present work, we have di...

show abstract

“…PTH is known to influence bone formation in various ways (1). In cultured cells, PTH decreases the production of type I collagen (2) and can enhance the synthesis of noncollagenous proteins, including osteocalcin (3,4) and interstitial collagenase (collagenase 3; ref. 5).…”

Section: Introductionmentioning

confidence: 99%

“…The increase in osteoblast number in the absence of the PTH/PTHrP receptor may reflect the action of PTH to suppress bone nodule formation in vitro (32). The increased matrix in the PTH/PTHrP-R -/-bones may reflect the action of PTH to decrease type I collagen synthesis in vitro (2). PTH/PTHrP-R -/-mice, but not PTHrP -/-mice, also exhibit decreased expression of osteopontin, osteocalcin, and collagenase 3 mRNA (19).…”

mentioning

confidence: 99%

Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development

Lanske

Amling²,

Neff³

et al. 1999

J. Clin. Invest.

223

129

View full text Add to dashboard Cite

The formation of the skeleton depends on the differentiation, function, and interaction of various cell types. Two distinct developmental patterns occur. Most bones are formed by endochondral ossification, in which a cartilage mold is replaced by bone. First, mesenchymal cells condense and differentiate into chondrocytes. The chondrocytes in the center of the shaft become hypertrophic and synthesize a distinct extracellular matrix that rapidly becomes mineralized. Osteoclasts then resorb this matrix, allowing blood vessel invasion, and osteoblasts bind to the cartilaginous matrix remnants and deposit bone matrix around them. Later, the remnants are removed and replaced by bone matrix. At the ends of the bone, the epiphyseal growth plates are formed when chondrocytes nearest the ends of bones proliferate and then undergo hypertrophy. A second process by which bone is formed is intramembranous ossification, in which matrix is deposited directly in the mesenchyme by osteoblasts, without replacement of a cartilage matrix. In the long bones, bone collar osteoblasts first participate in intramembranous ossification in the mesenchyme adjacent to the most hypertrophic chondrocytes.Many signaling systems control bone formation. The PTH/PTHrP receptor is at the center of one such system. This receptor integrates signals from both the calciumregulating hormone parathyroid hormone (PTH) and the paracrine factor parathyroid hormone-related protein (PTHrP). PTH is known to influence bone formation in various ways (1). In cultured cells, PTH decreases the production of type I collagen (2) and can enhance the synthesis of noncollagenous proteins, including osteocalcin (3, 4) and interstitial collagenase (collagenase 3; ref. 5). PTH can decrease both the proliferation of osteoblasts (6) and the formation of bone nodules from osteoprogenitor cells in vitro (7). On the other hand, in vivo PTH can increase bone formation, particularly when administered intermittently, and in trabecular bone (8). While the effects of PTHrP on osteoblasts are poorly characterized, the effects of PTHrP on growth plate chondrocytes have been demonstrated by the phenotype of the PTHrP -/-mouse (9). This phenotype shows that PTHrP slows the differentiation of chondrocytes in the growth plate (10).The PTH/PTHrP receptor is found in cells of the kidney tubule and in chondrocytes and osteoblasts of bone (11), and thus might mediate many actions of both PTH and PTHrP. However, other putative receptors for both ligands have been found (12-17), and one has been cloned (18). That the PTH/PTHrP receptor mediates the calcium-regulating action of PTH has been demonstrated by the inability of PTH to stimulate 45 Ca release from calvariae Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) bind to and activate the same PTH/PTHrP receptor. Deletion of either the PTHrP gene or the PTH/PTHrP receptor gene leads to acceleration of differentiation of growth plate chondrocytes. To explore further the functional relationships of PTHrP and the PTH/PTH...

show abstract

Parathyroid hormone alters collagen synthesis and procollagen mRNA levels in fetal rat calvaria.

Cited by 118 publications

References 23 publications

Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts.

Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts.

Parathyroid Hormone Regulates the Rat Collagenase-3 Promoter in Osteoblastic Cells through the Cooperative Interaction of the Activator Protein-1 Site and the runt Domain Binding Sequence

Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development

Contact Info

Product

Resources

About