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https://www.readbyqxmd.com/read/28445262/dose-dependence-of-pth-related-peptide-1-on-the-osteogenic-induction-of-mc3t3-e1-cells-in-vitro
#1
Jianping Wang, Jingfeng Li, Liang Yang, Yichi Zhou, Yi Wang
Parathyroid hormone (PTH), an 84-amino acid peptide, is an endocrine hormone that is secreted by parathyroid glands. PTH performs important functions in calcium regulation and bone remodeling. The PTH (1-34) named teriparatide, a 34-amino acid peptide derived from the N-terminus of PTH, conserves most of the functions of PTH, specifically the osteogenic capability. However, teriparatide is only used by injection and exhibits short duration. In addition, this PTH could not thoroughly expose active sites. In this study, a novel PTH-related peptide (designated PTHrP-1) derived from the N-terminus of PTH was added into the complete medium at different concentrations of PTHrP-1 (0, 50, 100, and 200 ng/mL) to induce the MC3T3-E1 cells...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28408247/absence-of-pthrp-nuclear-localization-and-c-terminus-sequences-leads-to-abnormal-development-of-t-cells
#2
Kun-Zhi Jia, Shu-Lei Jin, Chun Yao, Rong Rong, Chong Wang, Pan Du, Wen-Hui Jiang, Xiao-Feng Huang, Qin-Gang Hu, Deng-Shun Miao, Zi-Chun Hua
Parathyroid hormone-related protein (PTHrP), a ubiquitously expressed protein, is composed of four functional domains including N-terminus, mid region, nuclear localization signal (NLS) and C-terminus. Under the direction of NLS, PTHrP can enter cell nucleus from cytoplasm and stimulate mitogenesis. Although PTHrP is considered to have important developmental roles, the role of PTHrP NLS and C-terminus in developmental process remains unknown, especially in T-cell development. Here, we used a knock-in mouse model, which expresses a truncated form of PTHrP missing the NLS (87-107aa) and C-terminus (107-139aa) of the protein, to examine the role of PTHrP NLS and C-terminus in T-cell development...
April 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28403647/parathyroid-hormone-related-peptide-a-novel-endocrine-cardioprotective-conditioning-mimetic
#3
Tanuka Datta, Karin Przyklenk, Nabanita S Datta
An as-yet limited body of evidence suggests that calcium-regulating endocrine hormones-in particular, parathyroid hormone-related peptide (PTHrP)-may have unappreciated cardioprotective effects. The current review focuses on the concept that PTHrP may, via modulation of classic cardioprotective signaling pathways, provide a novel strategy to attenuate myocardial ischemia-reperfusion injury.
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28385776/rsk-activation-via-erk-modulates-human-colon-cancer-cells-response-to-pthrp
#4
Natalia Calvo, Pedro Carriere, Maria Julia Martin, Claudia Gentili
Parathyroid Hormone-related Peptide (PTHrP) is associated with several human cancers such as colon carcinoma. This disease is a complex multistep process that involves enhanced cell cycle progression and migration. Recently we obtained evidence that in the human colorectal adenocarcinoma Caco-2 cells, exogenous PTHrP increases the proliferation and positively modulates cell cycle progression via ERK1/2, p38 MAPK and PI3K. The purpose of this study was to explore if the serine/threonine kinase RSK, which is involved in the progress of many cancers and it is emerging as a potential therapeutic target, mediates PTHrP effects on cancer colon cells...
April 6, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28373577/parathyroid-hormone-controls-paracellular-ca-2-transport-in-the-thick-ascending-limb-by-regulating-the-tight-junction-protein-claudin14
#5
Tadatoshi Sato, Marie Courbebaisse, Noriko Ide, Yi Fan, Jun-Ichi Hanai, Jovana Kaludjerovic, Michael J Densmore, Quan Yuan, Hakan R Toka, Martin R Pollak, Jianghui Hou, Beate Lanske
Renal Ca(2+) reabsorption is essential for maintaining systemic Ca(2+) homeostasis and is tightly regulated through the parathyroid hormone (PTH)/PTHrP receptor (PTH1R) signaling pathway. We investigated the role of PTH1R in the kidney by generating a mouse model with targeted deletion of PTH1R in the thick ascending limb of Henle (TAL) and in distal convoluted tubules (DCTs): Ksp-cre;Pth1r(fl/fl) Mutant mice exhibited hypercalciuria and had lower serum calcium and markedly increased serum PTH levels. Unexpectedly, proteins involved in transcellular Ca(2+) reabsorption in DCTs were not decreased...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28370412/pthrp-12-48-modulates-the-bone-marrow-microenvironment-and-suppresses-human-osteoclast-differentiation-and-lifespan
#6
Archana Kamalakar, Charity L Washam, Nisreen S Akel, Bethany J Allen, Diarra K Williams, Frances L Swain, Kim Leitzel, Alan Lipton, Dana Gaddy, Larry J Suva
Bone is a common site for metastasis in breast cancer patients and is associated with a series of complications which significantly compromise patient survival, partially due to the advanced stage of disease at the time of detection. Currently, no clinically-approved biomarkers can identify or predict the development of bone metastasis. We recently identified a unique peptide fragment of parathyroid hormone-related protein (PTHrP), PTHrP(12-48), as a validated serum biomarker in breast cancer patients that correlates with and predicts the presence of bone metastases...
March 29, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28368420/matrix-metalloproteinase-processing-of-pthrp-yields-a-selective-regulator-of-osteogenesis-pthrp1-17
#7
J S Frieling, G Shay, V Izumi, S T Aherne, R G Saul, M Budzevich, J Koomen, C C Lynch
Parathyroid hormone-related protein (PTHrP) is a critical regulator of bone resorption and augments osteolysis in skeletal malignancies. Here we report that the mature PTHrP1-36 hormone is processed by matrix metalloproteinases to yield a stable product, PTHrP1-17. PTHrP1-17 retains the ability to signal through PTH1R to induce calcium flux and ERK phosphorylation but not cyclic AMP production or CREB phosphorylation. Notably, PTHrP1-17 promotes osteoblast migration and mineralization in vitro, and systemic administration of PTHrP1-17 augments ectopic bone formation in vivo...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28342003/lung-carcinoma-progression-and-survival-versus-amino-and-carboxyl-parathyroid-hormone-related-protein-expression
#8
Randolph H Hastings, Philippe R Montgrain, Rick A Quintana, Boris Chobrutskiy, Ashkhan Davani, Atsushi Miyanohara, Sepi Mahooti
PURPOSE: Expression of the carboxyl PTHrP region of parathyroid hormone-related protein (PTHrP) is a positive prognostic indicator in women with lung cancer, but amino PTHrP is a negative indicator in other lung cancer patients. This project investigated whether PTHrP could be expressed as predominantly amino PTHrP or carboxyl PTHrP in individual lung carcinomas. It also assessed domain-specific effects on cancer progression and patient survival. METHODS: PTHrP immunoreactivities were analyzed versus survival in a human lung cancer tissue microarray (TMA)...
March 25, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28331027/malignant-hypercalcaemia-related-to-parathyroid-hormone-related-peptide-pthrp-secretion-from-a-metastatic-pancreatic-neuroendocrine-tumour-net
#9
Megan Symington, Louise Davies, Gregory Kaltsas, Martin O Weickert
A 54-year-old woman presented to our centre with acute abdominal pain and vomiting. Routine blood tests showed severe hypercalcaemia (>4 mmol/L). Serum parathyroid hormone (PTH) was suppressed. CT scan detected a pancreatic mass and some liver lesions, initially suspicious for metastatic pancreatic adenocarcinoma. Liver biopsy however revealed the presence of a well-differentiated, grade 1, metastatic neuroendocrine tumour (NET) where prognosis is considerably better. Serum PTHrP was raised, indicating paraneoplastic hypercalcaemia, most likely secondary to the pancreatic NET...
March 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28323910/progressive-development-of-pth-resistance-in-patients-with-inactivating-mutations-on-the-maternal-allele-of-gnas
#10
Alessia Usardi, Asmaa Mamoune, Elodie Nattes, Jean-Claude Carel, Anya Rothenbuhler, Agnès Linglart
Background: PTH resistance is characterized by hypocalcaemia, hyperphosphatemia and elevated PTH in absence of vitamin D deficiency. Pseudohypoparathyroidism (PHP) type 1A (or iPPSD2, inactivating Signaling PTH/PTHrp Disorder 2 according to the new classification) is caused by mutations in the maternal GNAS allele. Objective: To assess PTH resistance over time in 20 patients affected by iPPSD2 (PHP1A), diagnosed because of family history, ectopic ossification or short stature and carrying a GNAS mutation...
February 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28289136/estrogen-modulates-mesenchymal-epidermal-interactions-in-the-adult-nipple
#11
Hsing-Jung Wu, Ji Won Oh, Dan F Spandau, Sunil Tholpady, Jesus Diaz, Laura J Schroeder, Carlos D Offutt, Adam B Glick, Maksim V Plikus, Sachiko Koyama, John Foley
Maintenance of specialized epidermis requires signals from the underlying mesenchyme; however, specific pathways involved remain to be identified. By recombining cells from ventral skin of the K14-PTHrP transgenic mice with those from wild-type, we show that transgenic stroma is sufficient to reprogram wild-type keratinocytes into nipple-like epidermis. To identify candidate nipple-specific signaling factors, we compared gene expression signatures of sorted Pdgfrα-positive ventral K14-PTHrP and wild-type fibroblasts, identifying differentially-expressed transcripts of the WNT, HGF, TGFβ, IGF, BMP, FGF and estrogen signaling...
March 13, 2017: Development
https://www.readbyqxmd.com/read/28257332/parathyroid-hormone-stimulates-adipose-tissue-browning-a-pathway-to-muscle-wasting
#12
Sandhya S Thomas, William E Mitch
PURPOSE OF REVIEW: Studying organ-to-organ communications (i.e. crosstalk) uncovers mechanisms regulating metabolism in several tissues. What is missing is identification of mediators of different catabolic conditions contributing to losses of adipose and muscle tissues. Identifying mediators involved in organ-to-organ crosstalk could lead to innovative therapeutic strategies because several disorders such as chronic kidney disease (CKD), cancer cachexia, and other catabolic conditions share signals of worsening metabolism and increased risk of mortality...
May 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28242308/molecular-characterisation-and-expression-of-parathyroid-hormone-related-protein-in-the-caudal-neurosecretory-system-of-the-euryhaline-flounder-platichthys-flesus
#13
Weiqun Lu, Yingying Jin, Jinling Xu, Michael P Greenwood, Richard J Balment
Parathyroid hormone-related protein (PTHrP) is a hypercalcemic factor in fish, but the source of circulating PTHrP remains unclear. In this study investigation of the caudal neurosecretory system (CNSS), considered one of major sources of PTHrP in fish, provided valuable insights into this regulatory system. We report pthrpa and pthrpb gene cloning, characterization, expression, and responses to low salinity and hypocalcemia challenge in flounder. The pthrpa and pthrpb precursors, isolated from a European flounder CNSS library, consist of 166 and 192 amino acid residues, respectively, with an overall homology of approximately 59...
February 24, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28217023/metabolic-bone-disease-in-the-context-of-metastatic-neuroendocrine-tumor-differentiation-from-skeletal-metastasis-the-molecular-pet-ct-imaging-features-and-exploring-the-possible-etiopathologies-including-parathyroid-adenoma-men1-and-paraneoplastic-humoral
#14
Rohit Ranade, Sandip Basu
Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan...
January 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28203174/richter-s-syndrome-with-hypercalcemia-induced-by-tumor-associated-production-of-parathyroid-hormone-related-peptide
#15
Naoki Watanabe, Hajime Yasuda, Soji Morishita, Yasuo Aota, Junichi Tomomatsu, Masaru Tanaka, Akimichi Ohsaka, Norio Komatsu
Humoral hypercalcemia due to parathyroid hormone-related peptide (PTHrP) elevation is a well-known complication of various malignancies, but the situation is rare concerning hematological malignancies except for adult T-cell leukemia/lymphoma. We report a case of Richter's syndrome with humoral hypercalcemia, and demonstrate by reverse transcription polymerase chain reaction (RT-PCR) that peripheral blood PTHrP levels were 2,500-fold higher compared to healthy controls. PTHrP production by tumor cells in chronic lymphocytic leukemia (CLL) and Richter's syndrome has been previously demonstrated by nonquantitative methods such as immunohistochemistry and northern blot analysis, but this is the first report using the RT-PCR method...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28178186/exogenous-pthrp-repairs-the-damaged-fracture-healing-of-pthrp-mice-and-accelerates-fracture-healing-of-wild-mice
#16
Yinhe Wang, Xin Fang, Chun Wang, Congzhu Ding, Hua Lin, Anlong Liu, Lei Wang, Yang Cao
Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone-related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/- mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods...
February 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28168064/hypercalcemia-of-malignancy-in-thymic-carcinoma-evolving-mechanisms-of-hypercalcemia-and-targeted-therapies
#17
Cheng Cheng, Jose Kuzhively, Sanford Baim
Here we describe, to our knowledge, the first case where an evolution of mechanisms responsible for hypercalcemia occurred in undifferentiated thymic carcinoma and discuss specific management strategies for hypercalcemia of malignancy (HCM). Case Description. We report a 26-year-old male with newly diagnosed undifferentiated thymic carcinoma associated with HCM. Osteolytic metastasis-related hypercalcemia was presumed to be the etiology of hypercalcemia that responded to intravenous hydration and bisphosphonate therapy...
2017: Case Reports in Endocrinology
https://www.readbyqxmd.com/read/28162969/parathyroid-hormone-directs-bone-marrow-mesenchymal-cell-fate
#18
Yi Fan, Jun-Ichi Hanai, Phuong T Le, Ruiye Bi, David Maridas, Victoria DeMambro, Carolina A Figueroa, Serkan Kir, Xuedong Zhou, Michael Mannstadt, Roland Baron, Roderick T Bronson, Mark C Horowitz, Joy Y Wu, John P Bilezikian, David W Dempster, Clifford J Rosen, Beate Lanske
Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28159062/abaloparatide-recombinant-human-pthrp-1-34-anabolic-therapy-for-osteoporosis
#19
REVIEW
Chee Kian Chew, Bart L Clarke
The treatment of osteoporosis is generally either by inhibition of bone resorption with antiresorptive agents or by stimulation of bone formation with anabolic agents. Currently, teriparatide (recombinant human parathyroid hormone 1-34 [rhPTH (1-34)]) is the only available approved anabolic agent in the U.S. Other anabolic agents are under investigation however. Abaloparatide is recombinant human parathyroid hormone-related peptide 1-34. This agent is an anabolic agent that appears more potent than teriparatide, and it may have more rapid onset of fracture reduction than teriparatide...
March 2017: Maturitas
https://www.readbyqxmd.com/read/28116542/the-hedgehog-signaling-pathway-is-repressed-during-the-osteogenic-differentiation-of-dental-follicle-cells
#20
C Morsczeck, A Reck, H C Beck
Dental follicle stem cells (DFCs) are precursor cells of alveolar osteoblasts, and previous studies have shown that the growth factor bone morphogenetic protein (BMP)2 induces the osteogenic differentiation of DFCs. However, the molecular mechanism down-stream of the induction of the osteogenic differentiation by BMP2 remains elusive. We investigated therefore the phosphoproteome of DFCs after the induction of the osteogenic differentiation with BMP2. In this study, phosphoproteins of the hedgehog "off" state were differentially expressed...
April 2017: Molecular and Cellular Biochemistry
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