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https://www.readbyqxmd.com/read/28526527/cellular-scale-model-of-growth-plate-an-in-silico-model-of-chondrocyte-hypertrophy
#1
H A Castro-Abril, J M Guevara, M A Moncayo, S J Shefelbine, L A Barrera, D A Garzón-Alvarado
The growth plate is the responsible for longitudinal bone growth. It is a cartilaginous structure formed by chondrocytes that are continuously undergoing a differentiation process that starts with a highly proliferative state, followed by cellular hypertrophy, and finally tissue ossification. Within the growth plate chondrocytes display a characteristic columnar organization that potentiates longitudinal growth. Both chondrocyte organization and hypertrophy are highly regulated processes influenced by biochemical and mechanical stimuli...
May 16, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28525313/a-tunable-three-dimensional-in-vitro-culture-model-of-growth-plate-cartilage-using-alginate-hydrogel-scaffolds
#2
Alek G Erickson, Taylor D Laughlin, Sarah M Romereim, Catherine N Sargus-Patino, Angela K Pannier, Andrew T Dudley
Defining the final size and geometry of engineered tissues through precise control of the scalar and vector components of tissue growth is a necessary benchmark for regenerative medicine, but it has proved to be a significant challenge for tissue engineers. The growth plate cartilage that promotes elongation of the long bones is a good model system for studying morphogenetic mechanisms because cartilage is composed of a single cell type, the chondrocyte; chondrocytes are readily maintained in culture; and growth trajectory is predominately in a single vector...
May 18, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28521692/pharmacological-treatment-of-bone-loss
#3
Rui Pang, Weibo Xia
Bone loss is common in clinical practice, such as health assessment of postmenopausal women, treatment of tumor metastasis, side-effects of glucocorticoids, and skeletal manifestations of inflammatory diseases. The imbalance of remodeling between bone resorption and bone formation, the pathophysiological basis of bone loss, increases bone fragility. The treatment of bone loss is mainly carried out from the treatment of osteoporosis. There are various pharmacological therapies for bone loss, which will be introduced in 3 aspects, including anti-resorptive agents, anabolic agents and new medications...
May 16, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28470757/osteocytes-acidify-their-microenvironment-in-response-to-pthrp-in-vitro-and-in-lactating-mice-in-vivo
#4
Katharina Jähn, Shilpa Kelkar, Hong Zhao, Yixia Xie, LeAnn M Tiede-Lewis, Vladimir Dusevich, Sarah L Dallas, Lynda F Bonewald
Osteocytes appear to mobilize calcium within minutes in response to PTH injections and we have previously shown that osteocytes remove their perilacunar matrix during lactation through activation of the PTH type 1 receptor. Mechanisms utilized by osteocytes to mobilize calcium are unknown but we hypothesized that the molecular components may be similar to those used by osteoclasts. Here we show, using IDG-SW3 cells that ATP6V0D2, an essential component of vacuolar ATPase in osteoclasts, and other genes associated with osteoclastic bone resorption increase with osteoblast to osteocyte differentiation...
May 4, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28459108/cachexia-brown-fat-a-burning-issue-in-cancer
#5
Serkan Kir, Bruce M Spiegelman
Cachexia, a progressive weight loss in cancer patients that results from tumor-induced energy wasting, is a serious problem that interferes with response to treatment and affects quality of life. Recent studies suggest that thermogenesis of adipose tissues is involved in energy wasting and also point to a link between the atrophy of fat and muscle. Tumor-derived PTHrP has emerged as a key molecule playing multiple roles in cachexia, from fat "browning" factor to potential therapeutic target.
September 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28445262/dose-dependence-of-pth-related-peptide-1-on-the-osteogenic-induction-of-mc3t3-e1-cells-in-vitro
#6
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
#7
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
#8
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
#9
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
#10
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
#11
Archana Kamalakar, Charity L Washam, Nisreen S Akel, Bethany J Allen, Diarra K Williams, Frances L Swain, Kim Leitzel, Allan 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 that 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
#12
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
#13
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
#14
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
#15
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-mesenchyme-epidermis-interactions-in-the-adult-nipple
#16
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, the specific pathways involved remain to be identified. By recombining cells from the ventral skin of the K14-PTHrP transgenic mice [which overexpress parathyroid hormone-related protein (PTHrP) in their developing epidermis and mammary glands] 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 that are involved in WNT, HGF, TGFβ, IGF, BMP, FGF and estrogen signaling...
April 15, 2017: Development
https://www.readbyqxmd.com/read/28257332/parathyroid-hormone-stimulates-adipose-tissue-browning-a-pathway-to-muscle-wasting
#17
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
#18
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
#19
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
#20
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
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