scholarly journals Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme

Development ◽  
2012 ◽  
Vol 139 (22) ◽  
pp. 4239-4249 ◽  
Author(s):  
M. Hiremath ◽  
P. Dann ◽  
J. Fischer ◽  
D. Butterworth ◽  
K. Boras-Granic ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Wnt Signaling ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Mammary Mesenchyme

Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 513-525 ◽  
Author(s):  
J. Foley ◽  
P. Dann ◽  
J. Hong ◽  
J. Cosgrove ◽  
B. Dreyer ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Mesenchymal Cells ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Mammary Mesenchyme ◽  
Pthrp Receptor

Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regulates a series of cell fate decisions that are central to the survival and morphogenesis of the mammary epithelium and the formation of the nipple. PTHrP is made in the epithelial cells of the mammary bud and, during embryonic mammary development, it interacts with the surrounding mesenchymal cells to induce the formation of the dense mammary mesenchyme. In response, these mammary-specific mesenchymal cells support the maintenance of mammary epithelial cell fate, trigger epithelial morphogenesis and induce the overlying epidermis to form the nipple. In the absence of PTHrP signaling, the mammary epithelial cells revert to an epidermal fate, no mammary ducts are formed and the nipple does not form. In the presence of diffuse epidermal PTHrP signaling, the ventral dermis is transformed into mammary mesenchyme and the entire ventral epidermis becomes nipple skin. These alterations in cell fate require that PTHrP be expressed during development and they require the presence of the PTH/PTHrP receptor. Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and (β)-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways.

scholarly journals Melatonin Contributes to The Hypertrophic Differentiation of Mesenchymal Stem Cell-Derived Chondrocytes Via Activation of The WNT/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
Xuan Wang ◽  
Tianwei He ◽  
Lei He ◽  
Bu Yang ◽  
Zhongyu Liu ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Terminal Differentiation ◽  
Related Protein ◽  
Rt Pcr ◽  
Type X Collagen ◽  
Parathyroid Hormone Related Protein ◽  
Histological Staining

Abstract BackgroundHypertrophy is a critical process for chondrocyte differentiation and maturation during endochondral ossification, which is responsible for the formation of long bone and its postnatal longitudinal growth. Increasing evidence suggests that melatonin, an indole hormone, plays a pivotal role in chondrogenesis; however, little is known about its effects on the terminal differentiation of chondrocytes. MethodsMesenchymal stem cells (MSCs) derived chondrocytes generated by a high-density micromass culture system were further induced to hypertrophic differentiation. The melatonin-mediated hypertrophic differentiation were examined by reverse transcription polymerase chain reaction analysis (RT-PCR) analysis and histological staining and immunohistochemistry. The expression of downstream factors of WNT signaling pathway was evaluated by RT-PCR, western blotting and immunofluorescence. The WNT signaling pathway antagonist XAV-939 was used to further demonstrate melatonin-induced hypertrophic chondrocytes and WNT signaling pathway activation.ResultsHistological staining showed melatonin increased the chondrocytes cell volume and the expression of type X collagen, but decreased the expression of type II collagen compare to the control group. RT-PCR showed that melatonin significantly up-regulated the expression of biomarkers of hypertrophic chondrocytes, including type X collagen (COL10A1), alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), Indian hedgehog (IHH), and parathyroid hormone-related protein receptor (PTHrP-R) and down-regulated the hallmarks of chondrocytes, including parathyroid hormone-related protein (PTHrP). The WNT signaling pathway PCR array showed that the effect of melatonin was accompanied by the up-regulation of multiple target genes of the canonical WNT signaling pathway and the melatonin-mediated effect can be blocked by XAV-939. ConclusionsThese findings demonstrate that melatonin can enhance the hypertrophic differentiation of MSCs-derived chondrocytes through the WNT signaling pathway. It adds evidence to the role of melatonin in promoting bone development and highlights its positive effects on chondrocytes terminal differentiation.

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.

Parathyroid Hormone–Related Protein Inhibits Endothelin-1 Production

Hypertension ◽  
1996 ◽  
Vol 27 (3) ◽  
pp. 360-363 ◽  
Author(s):  
Bingbing Jiang ◽  
Shigeto Morimoto ◽  
Keisuke Fukuo ◽  
Atsushi Hirotani ◽  
Michio Tamatani ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Endothelin 1 ◽  
Parathyroid Hormone Related Protein

Parathyroid Hormone–Related Protein Upregulates Interleukin-1β–Induced Nitric Oxide Synthesis

Hypertension ◽  
1997 ◽  
Vol 30 (4) ◽  
pp. 922-927 ◽  
Author(s):  
Bingbing Jiang ◽  
Shigeto Morimoto ◽  
Jin Yang ◽  
Keisuke Fukuo ◽  
Atsushi Hirotani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parathyroid Hormone ◽  
Interleukin 1Β ◽  
Nitric Oxide Synthesis ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

scholarly journals Purification and Characterization of Recombinant Human Parathyroid Hormone-related Protein

1989 ◽  
Vol 264 (25) ◽  
pp. 14806-14811
Author(s):  
R G Hammonds ◽  
P McKay ◽  
G A Winslow ◽  
H Diefenbach-Jagger ◽  
V Grill ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Human Parathyroid Hormone ◽  
Purification And Characterization ◽  
Parathyroid Hormone Related Protein
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