scholarly journals Sox9 Family Members Negatively Regulate Maturation and Calcification of Chondrocytes through Up-Regulation of Parathyroid Hormone–related Protein

2009 ◽  
Vol 20 (21) ◽  
pp. 4541-4551 ◽  
Author(s):  
Katsuhiko Amano ◽  
Kenji Hata ◽  
Atsushi Sugita ◽  
Yoko Takigawa ◽  
Koichiro Ono ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Endochondral Ossification ◽  
Family Members ◽  
Chondrocyte Differentiation ◽  
Related Protein ◽  
Primary Chondrocytes ◽  
Chondrocyte Maturation ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression ◽  
Late Stages

Sox9 is a transcription factor that plays an essential role in chondrogenesis and has been proposed to inhibit the late stages of endochondral ossification. However, the molecular mechanisms underlying the regulation of chondrocyte maturation and calcification by Sox9 remain unknown. In this study, we attempted to clarify roles of Sox9 in the late stages of chondrocyte differentiation. We found that overexpression of Sox9 alone or Sox9 together with Sox5 and Sox6 (Sox5/6/9) inhibited the maturation and calcification of murine primary chondrocytes and up-regulated parathyroid hormone–related protein (PTHrP) expression in primary chondrocytes and the mesenchymal cell line C3H10T1/2. Sox5/6/9 stimulated the early stages of chondrocyte proliferation and development. In contrast, Sox5/6/9 inhibited maturation and calcification of chondrocytes in organ culture. The inhibitory effects of Sox5/6/9 were rescued by treating with anti-PTHrP antibody. Moreover, Sox5/6/9 bound to the promoter region of the PTHrP gene and up-regulated PTHrP gene promoter activity. Interestingly, we also found that the Sox9 family members functionally collaborated with Ihh/Gli2 signaling to regulate PTHrP expression and chondrocyte differentiation. Our results provide novel evidence that Sox9 family members mediate endochondral ossification by up-regulating PTHrP expression in association with Ihh/Gli2 signaling.

Dexamethasone regulation of parathyroid hormone-related protein (PTHrP) expression in a squamous cancer cell line

1994 ◽  
Vol 101 (1-2) ◽  
pp. 295-306 ◽  
Author(s):  
Jane A. Glatz ◽  
Joan K. Heath ◽  
Justine Southby ◽  
Leonie M. O'Keeffe ◽  
Kiriyama Takeshi ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Squamous Cancer ◽  
Pthrp Expression

Parathyroid hormone-related protein induction in focal stroke: a neuroprotective vascular peptide

2003 ◽  
Vol 284 (4) ◽  
pp. R1021-R1030 ◽  
Author(s):  
Janet L. Funk ◽  
Elton Migliati ◽  
Guanjie Chen ◽  
Hongbing Wei ◽  
Jonathan Wilson ◽  
...  
Keyword(s):  
Blood Flow ◽  
Parathyroid Hormone ◽  
Cell Injury ◽  
Tissue Injury ◽  
Northern Analysis ◽  
Related Protein ◽  
Cerebral Microvessels ◽  
Ischemic Brain ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression

Parathyroid hormone-related protein (PTHrP) is a multifunctional peptide that enhances blood flow in non-central nervous system (CNS) vascular beds by causing vasodilation. PTHrP expression is induced in non-CNS organs in response to ischemia. Experiments were therefore undertaken to determine whether PTHrP can be induced in brain in response to ischemic injury and whether PTHrP can act locally as a vasodilator in the cerebral vasculature, an effect that could be neuroprotective in the setting of stroke. PTHrP expression was examined by Northern analysis and immunohistochemical staining in male Sprague-Dawley rats subjected to permanent middle cerebral artery occlusion (MCAO). Vasodilatory effects of superfused PTHrP(1–34) on pial arterioles were determined by intravital fluorescence microscopy. Effects of PTHrP(1–34) peptide administration on MCAO infarction size reduction were assessed. PTHrP expression was induced in the ischemic hemisphere as early as 4 h after MCAO and remained elevated for up to 24 h. Increased immunoreactive PTHrP at sites of ischemic tissue injury was located in the cerebral microvessels. Superfusion with PTHrP(1–34) peptide for up to 25 min increased pial arteriolar diameter by 30% in normal animals. In animals with permanent MCAO, PTHrP(1–34) peptide treatment significantly decreased cortical infarct size (−47%). In summary, PTHrP expression increases at sites of ischemic brain injury in the cerebrovasculature. This local increase in PTHrP could be an adaptive response that enhances blood flow to the ischemic brain, thus limiting cell injury.

Parathyroid hormone-related protein (PTHrp) expression in human bone metastases (BM)

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 9696-9696 ◽  
Author(s):  
L. Costa ◽  
A. Fernandes ◽  
A. G. Oliveira ◽  
K. Leitzel ◽  
S. Ali ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Metastases ◽  
Human Bone ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression

Parathyroid hormone-related protein reduces alveolar epithelial cell proliferation during lung injury in rats

2000 ◽  
Vol 279 (1) ◽  
pp. L194-L200 ◽  
Author(s):  
Randolph H. Hastings ◽  
John T. Berg ◽  
Daphne Summers-Torres ◽  
Douglas W. Burton ◽  
Leonard J. Deftos
Keyword(s):  
Cell Proliferation ◽  
Parathyroid Hormone ◽  
Lung Injury ◽  
Alveolar Epithelial Cell ◽  
Epithelial Cell Proliferation ◽  
Related Protein ◽  
High Power Field ◽  
Alveolar Epithelial ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression

Parathyroid hormone-related protein (PTHrP) is a growth inhibitor for alveolar type II cells and could be a regulatory factor for alveolar epithelial cell proliferation after lung injury. We investigated lung PTHrP expression in rats exposed to 85% oxygen. Lung levels of PTHrP were significantly decreased between 4 and 8 days of hyperoxia, concurrent with increased expression of proliferating cell nuclear antigen and increased incorporation of 5-bromo-2′-deoxyuridine (BrdU) into DNA in lung corner cells. PTHrP receptor was present in both normal and hyperoxic lung. To test whether the fall in PTHrP was related to cell proliferation, we instilled PTHrP into lungs on the fourth day of hyperoxia. Eight hours later, BrdU labeling in alveolar corner cells was 3.2 ± 0.4 cells/high-power field in hyperoxic PBS-instilled rats compared with 0.5 ± 0.3 cells/high-power field in PTHrP-instilled rats ( P < 0.01). Thus PTHrP expression changes in response to lung injury due to 85% oxygen and may regulate cell proliferation.

scholarly journals Parathyroid hormone-related protein (PTHrP) mRNA splicing and parathyroid hormone/PTHrP receptor mRNA expression in human placenta and fetal membranes

1998 ◽  
Vol 21 (2) ◽  
pp. 225-234 ◽  
Author(s):  
NE Curtis ◽  
RJ Thomas ◽  
MT Gillespie ◽  
RG King ◽  
GE Rice ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Mrna Expression ◽  
Late Pregnancy ◽  
Mrna Splicing ◽  
Fetal Membranes ◽  
Related Protein ◽  
Receptor Mrna ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression ◽  
Pthrp Receptor

During human pregnancy, parathyroid hormone-related protein (PTHrP) and parathyroid hormone (PTH)/PTHrP receptor are produced by the uterus, placenta, fetal membranes (amnion and chorion) and developing fetus. PTHrP alternative 3' mRNA splicing results in transcripts which encode three PTHrP isoforms and have been identified in amnion. Uteroplacental PTHrP expression is greatest in amnion and increases dramatically during late pregnancy. The aims of this study were to determine PTH/PTHrP receptor mRNA expression at preterm and term gestations and to determine 3' alternative splicing patterns in placenta, amnion and choriodecidua at preterm and term gestations. Using semiquantitative reverse transcription-polymerase chain reaction, PTHrP and PTH/PTHrP receptor transcripts were identified in preterm (n=5) and term (n=7) gestational tissues. PTH/PTHrP receptor mRNA expression did not differ between tissue types or change with advancing gestation. In contrast, PTHrP expression in the same tissues increased with advancing gestation and was significantly greater in amnion than in placenta and choriodecidua. Thus PTHrP, although produced predominantly in amnion, may act in amnion and other tissues including placenta, choriodecidua and myometrium. In amnion over placenta, transcripts encoding PTHrP 1-139 and 1-173 were detected in some preterm and all term samples and those encoding PTHrP 1-141 were detected in all samples. Similar results were obtained for reflected amnion. In placenta and choriodecidua, PTHrP 1-139 and 1-173 transcripts were undetectable or of low abundance. PTHrP 1-141 transcripts were detected in some placenta and choriodecidua samples. In summary, transcripts encoding PTHrP 1-141 appeared to be more abundantly expressed than those encoding PTHrP 1-139 or 1-173. However, the up-regulation of PTHrP expression in amnion at term may involve each of the alternative 3' mRNA splicing pathways since transcripts for each isoform appeared to be more consistently expressed at term.

scholarly journals Mammary gland serotonin regulates parathyroid hormone-related protein and other bone-related signals

2012 ◽  
Vol 302 (8) ◽  
pp. E1009-E1015 ◽  
Author(s):  
Laura L. Hernandez ◽  
Karen A. Gregerson ◽  
Nelson D. Horseman
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Related Protein ◽  
Bone Demineralization ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression

Breast cells drive bone demineralization during lactation and metastatic cancers. A shared mechanism among these physiological and pathological states is endocrine secretion of parathyroid hormone-related protein (PTHrP), which acts through osteoblasts to stimulate osteoclastic bone demineralization. The regulation of PTHrP has not been accounted for fully by any conventional mammotropic stimuli or tumor growth factors. Serotonin (5-HT) synthesis within breast epithelial cells is induced during lactation and in advancing breast cancer. Here we report that serotonin deficiency (knockout of tryptophan hydroxylase-1) results in a reduction of mammary PTHrP expression during lactation, which is rescued by restoring 5-HT synthesis. 5-HT induced PTHrP expression in lactogen-primed mammary epithelial cells from either mouse or cow. In human breast cancer cells 5-HT induced both PTHrP and the metastasis-associated transcription factor Runx2/Cbfa1. Based on receptor expression and pharmacological evidence, the 5-HT2 receptor type was implicated as being critical for induction of PTHrP and Runx2. These results connect 5-HT synthesis to the induction of bone-regulating factors in the normal mammary gland and in breast cancer cells.

Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3485-3493
Author(s):  
M.E. Dunbar ◽  
P.R. Dann ◽  
G.W. Robinson ◽  
L. Hennighausen ◽  
J.P. Zhang ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cell Fate ◽  
Ectopic Expression ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Related Protein ◽  
Cell Fate Decisions ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression ◽  
Mammary Mesenchyme

Male mice lack mammary glands due to the interaction of circulating androgens with local epithelial-mesenchymal signaling in the developing mammary bud. Mammary epithelial cells induce androgen receptor (AR) within the mammary mesenchyme and, in response to androgens, the mesenchyme condenses around the epithelial bud, destroying it. We show that this process involves apoptosis and that, in the absence of parathyroid hormone-related protein (PTHrP) or its receptor, the PTH/PTHrP receptor (PPR1), it fails due to a lack of mesenchymal AR expression. In addition, the expression of tenascin C, another marker of the mammary mesenchyme, is also dependent on PTHrP. PTHrP expression is initiated on E11 and, within the ventral epidermis, is restricted to the forming mammary epithelial bud. In contrast, PPR1 expression is not limited to the mammary bud, but is found generally within the subepidermal mesenchyme. Finally, transgenic overexpression of PTHrP within the basal epidermis induces AR and tenasin C expression within the ventral dermis, suggesting that ectopic expression of PTHrP can induce the ventral mesenchyme to express mammary mesenchyme markers. We propose that PTHrP expression specifically within the developing epithelial bud acts as a dominant signal participating in cell fate decisions leading to a specialized mammary mesenchyme.

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