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https://www.readbyqxmd.com/read/28077677/pharmacological-rescue-of-diabetic-skeletal-stem-cell-niches
#1
Ruth Tevlin, Eun Young Seo, Owen Marecic, Adrian McArdle, Xinming Tong, Bryan Zimdahl, Andrey Malkovskiy, Rahul Sinha, Gunsagar Gulati, Xiyan Li, Taylor Wearda, Rachel Morganti, Michael Lopez, Ryan C Ransom, Christopher R Duldulao, Melanie Rodrigues, Allison Nguyen, Michael Januszyk, Zeshaan Maan, Kevin Paik, Kshemendra-Senarath Yapa, Jayakumar Rajadas, Derrick C Wan, Geoffrey C Gurtner, Michael Snyder, Philip A Beachy, Fan Yang, Stuart B Goodman, Irving L Weissman, Charles K F Chan, Michael T Longaker
Diabetes mellitus (DM) is a metabolic disease frequently associated with impaired bone healing. Despite its increasing prevalence worldwide, the molecular etiology of DM-linked skeletal complications remains poorly defined. Using advanced stem cell characterization techniques, we analyzed intrinsic and extrinsic determinants of mouse skeletal stem cell (mSSC) function to identify specific mSSC niche-related abnormalities that could impair skeletal repair in diabetic (Db) mice. We discovered that high serum concentrations of tumor necrosis factor-α directly repressed the expression of Indian hedgehog (Ihh) in mSSCs and in their downstream skeletogenic progenitors in Db mice...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077400/differential-expression-of-hedgehog-and-snail-in-cutaneous-fibrosing-disorders-implications-for-targeted-inhibition
#2
Amrita Goyal, Katy R Linskey, Jonathan Kay, Lyn M Duncan, Rosalynn M Nazarian
OBJECTIVES: To examine Hedgehog signaling in cutaneous fibrosing disorders for which effective approved therapies are lacking, expand our knowledge of pathophysiology, and explore the rationale for targeted inhibition. METHODS: Stain intensity and percentage of cells staining for Sonic hedgehog (Shh), Indian hedgehog (Ihh), Patched (Ptch), glycogen synthase kinase 3 β (GSK3-β), β-catenin, and Snail were evaluated in human skin biopsy specimens of keloid, hypertrophic scar (Hscar), scleroderma, nephrogenic systemic fibrosis (NSF), scar, and normal skin using a tissue microarray...
December 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28068223/hepatocyte-taz-wwtr1-promotes-inflammation-and-fibrosis-in-nonalcoholic-steatohepatitis
#3
Xiaobo Wang, Ze Zheng, Jorge Matias Caviglia, Kathleen E Corey, Tina M Herfel, Bishuang Cai, Ricard Masia, Raymond T Chung, Jay H Lefkowitch, Robert F Schwabe, Ira Tabas
Nonalcoholic steatohepatitis (NASH) is a leading cause of liver disease worldwide. However, the molecular basis of how benign steatosis progresses to NASH is incompletely understood, which has limited the identification of therapeutic targets. Here we show that the transcription regulator TAZ (WWTR1) is markedly higher in hepatocytes in human and murine NASH liver than in normal or steatotic liver. Most importantly, silencing of hepatocyte TAZ in murine models of NASH prevented or reversed hepatic inflammation, hepatocyte death, and fibrosis, but not steatosis...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28064102/influence-of-components-of-tumour-microenvironment-on-the-response-of-hct-116-colorectal-cancer-to-the-ruthenium-based-drug-nami-a
#4
Alberta Bergamo, Chiara Pelillo, Angela Chambery, Gianni Sava
Solid tumours are constituted of tumour cells, healthy cells recruited from the host tissues and soluble factors released by both these cell types. The present investigation examines the capacity of co-cultures between the HCEC colon epithelial cells and the HCT-116 colorectal cancer cells (mimicking the primary site of tumour growth) and between IHH hepatocytes and the HCT-116 colorectal cancer cells (metastatic site) to influence the effects of NAMI-A (imidazolium trans-imidazoledimethylsulphoxidetetrachloro ruthenate) on the tumour cells themselves...
December 2, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28056292/-research-of-the-expression-of-subchondral-bone-of-indian-hedgehog-with-early-experimental-osteoarthritis-induced-by-mechanical-stress
#5
R K Zhang, G W Li, D W Zhang, B Yu, S Y Feng
Objective: To investigate the the expression of subchondral bone of Indian hedgehog(Ihh) with early experimental osteoarthritis induced by mechanical stress. Methods: The animals were equally divided into two groups: experimental group(E-group, n=15) and control group(S-group, n=15). The right knee joints of E-group underwent surgery, which involved in both medial collateral ligament (MCL) transaction and medial meniscectomy, while the control group was only carried out with a sham operation.The rats were killed at 1, 2 and 4 weeks postsurgery to obtain the right knee joints...
January 3, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28055425/igf1-regulates-runx1-expression-via-irs1-2-implications-for-antler-chondrocyte-differentiation
#6
Zhan-Qing Yang, Hong-Liang Zhang, Cui-Cui Duan, Shuang Geng, Kai Wang, Hai-Fan Yu, Zhan-Peng Yue, Bin Guo
Although IGF1 is important for the proliferation and differentiation of chondrocytes, its underlying molecular mechanism is still unknown. Here we addressed the physiological function of IGF1 in antler cartilage and explored the interplay of IGF1, IRS1/2 and RUNX1 in chondrocyte differentiation. The results showed that IGF1 was highly expressed in antler chondrocytes. Exogenous rIGF1 could increase the proliferation of chondrocytes and cell proportion in the S phase, whereas IGF1R inhibitor PQ401 abrogated the induction by rIGF1...
January 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28013369/peroxisomal-abnormalities-in-the-immortalized-human-hepatocyte-ihh-cell-line
#7
Femke C C Klouwer, Janet Koster, Sacha Ferdinandusse, Hans R Waterham
The immortalized human hepatocyte (IHH) cell line is increasingly used for studies related to liver metabolism, including hepatic glucose, lipid, lipoprotein and triglyceride metabolism, and the effect of therapeutic interventions. To determine whether the IHH cell line is a good model to investigate hepatic peroxisomal metabolism, we measured several peroxisomal parameters in IHH cells and, for comparison, HepG2 cells and primary skin fibroblasts. This revealed a marked plasmalogen deficiency and a deficient fatty acid α-oxidation in the IHH cells, due to a defect of PEX7, a cytosolic receptor protein required for peroxisomal import of a subset of peroxisomal proteins...
December 24, 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28008864/idiopathic-hypogonadothropic-hypogonadism-due-to-novel-fgfr1-mutations
#8
Gamze Akkuş, Damla Kotan, Erdem Durmaz, Eda Mengen, İhsan Turan, Ayça Ulubay, Fatih Gürbüz, Bilgin Yüksel, Tamer Tetiker, Ali Kemal Topaloğlu
OBJECTIVE: Underlying genetic etiology of Hypogonadothropic Hypogonadism (HH) is heterogenous. Fibroblast growth factor signaling is pivotal in the ontogeny of GnRH neurons. Loss of function mutations inFGFR1 gene cause variable hypogonadothropic hypogonadism phenotype encompassing pubertal delay to IHH or KS. As FGFR1 mutations are common, recognizing mutations and associated phenotypes may enhance clinical management. METHODS: Using a candidate gene approach we screened 52 IHH/KS patients...
December 23, 2016: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/27994624/regulatory-mechanisms-of-the-ihh-pthrp-signaling-pathway-in-fibrochondrocytes-in-entheses-of-pig-achilles-tendon
#9
Xuesong Han, Yanfeng Zhuang, Zhihong Zhang, Lin Guo, Wanming Wang
This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh)/parathyroid hormone-related protein (PTHrP) signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I), Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh signal blocking group was set up using Ihh signaling pathway-specific blocking agent cyclopamine...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27966732/a-de-novo-2q35-q36-1-deletion-incorporating-ihh-in-a-chinese-boy-47-xyy-with-syndactyly-type-iii-waardenburg-syndrome-and-congenital-heart-disease
#10
D Wang, G F Ren, H Z Zhang, C Y Yi, Z J Peng
Reports of terminal and interstitial deletions of the long arm of chromosome 2 are rare in the literature. Here, we present a case report concerning a Chinese boy with a 47,XYY karyotype and a de novo deletion comprising approximately 5 Mb between 2q35 and q36.1, along with syndactyly, type III Waardenburg syndrome, and congenital heart disease. High-resolution chromosome analysis to detect copy number variations was carried out using an Affymetrix microarray platform, and the genes affected by the patient's deletion, including IHH, were determined...
December 2, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27965056/porcupine-dependent-wnt-signaling-controls-stromal-proliferation-and-endometrial-gland-maintenance-through-the-action-of-distinct-wnts
#11
Omar Farah, Steffen Biechele, Janet Rossant, Daniel Dufort
Wnt signaling has been shown to be important in orchestrating proper development of the female reproductive tract. In the uterus, six members of the Wnt family are expressed in the neonatal endometrium and deletion of individual Wnt genes often leads to similar phenotypes, suggesting an interaction of these genes in uterine development and function. Furthermore, Wnts may have complementary functions, which could mask the identification of their individual functional role in single gene deletions. To circumvent this issue, we have generated a deletion of the Porcupine homolog within the female reproductive tract using progesterone receptor-Cre mice (Pgr(Cre/+)); preventing Wnt secretion from the producing cells...
December 10, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27935821/stromal-hedgehog-signaling-maintains-smooth-muscle-and-hampers-micro-invasive-prostate-cancer
#12
Zhaohui Yang, Yu-Ching Peng, Anuradha Gopalan, Dong Gao, Yu Chen, Alexandra L Joyner
It is widely appreciated that reactive stroma or carcinoma-associated fibroblasts can influence epithelial tumor progression. In prostate cancer (PCa), the second most common male malignancy worldwide, the amount of reactive stroma is variable and has predictive value for tumor recurrence. By analyzing human PCa protein and RNA expression databases, we found smooth muscle cells (SMCs) are decreased in advanced tumors, whereas fibroblasts are maintained. In three mouse models of PCa, we found the composition of the stroma is distinct...
November 30, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27930311/spop-promotes-skeletal-development-and-homeostasis-by-positively-regulating-ihh-signaling
#13
Hongchen Cai, Aimin Liu
Indian Hedgehog (Ihh) regulates chondrocyte and osteoblast differentiation through the Glioma-associated oncogene homolog (Gli) transcription factors. Previous in vitro studies suggested that Speckle-type POZ protein (Spop), part of the Cullin-3 (Cul3) ubiquitin ligase complex, targets Gli2 and Gli3 for degradation and negatively regulates Hedgehog (Hh) signaling. In this study, we found defects in chondrocyte and osteoblast differentiation in Spop-null mutant mice. Strikingly, both the full-length and repressor forms of Gli3, but not Gli2, were up-regulated in Spop mutants, and Ihh target genes Patched 1 (Ptch1) and parathyroid hormone-like peptide (Pthlh) were down-regulated, indicating compromised Hh signaling...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27904711/naringin-promotes-osteogenic-differentiation-of-bone-marrow-stromal-cells-by-up-regulating-foxc2-expression-via-the-ihh-signaling-pathway
#14
Fei-Xiang Lin, Shi-Xin Du, De-Zhong Liu, Qin-Xiao Hu, Guo-Yong Yu, Chu-Cheng Wu, Gui-Zhou Zheng, Da Xie, Xue-Dong Li, Bo Chang
Naringin is an active compound extracted from Rhizoma Drynariae, and studies have revealed that naringin can promote proliferation and osteogenic differentiation of bone marrow stromal cells (BMSCs). In this study, we explored whether naringin could promote osteogenic differentiation of BMSCs by upregulating Foxc2 expression via the Indian hedgehog (IHH) signaling pathway. BMSCs were cultured in basal medium, basal medium with naringin, osteogenic induction medium, osteogenic induction medium with naringin and osteogenic induction medium with naringin in the presence of the IHH inhibitor cyclopamine (CPE)...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27887870/involvement-of-indian-hedgehog-signaling-in-mesenchymal-stem-cell-augmented-rotator-cuff-tendon-repair-in-an-athymic-rat-model
#15
Jian-Chun Zong, Michael J Mosca, Ryan M Degen, Amir Lebaschi, Camila Carballo, Andrew Carbone, Guang-Ting Cong, Liang Ying, Xiang-Hua Deng, Scott A Rodeo
BACKGROUND: Bone marrow aspirate has been used in recent years to augment tendon-to-bone healing, including in rotator cuff repair. However, the healing mechanism in cell-based therapy has not been elucidated in detail. METHODS: Sixteen athymic nude rats were randomly allocated to 2 groups: experimental (human mesenchymal stem cells in fibrin glue carrier) and control (fibrin glue only). Animals were sacrificed at 2 and 4 weeks. Immunohistochemical staining was performed to evaluate Indian hedgehog (Ihh) signaling and SOX9 signaling in the healing enthesis...
November 22, 2016: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/27879963/hypogonadism-and-non-alcoholic-fatty-liver-disease
#16
Gesthimani Mintziori, Pavlos Poulakos, Christos Tsametis, Dimitrios G Goulis
Non-alcoholic fatty liver disease (NAFLD) is more common in men than in women. Thus, it has been suggested that sex steroids do have a role in the development of NAFLD. The aim of the current paper is to illustrate the association between NAFLD and hypogonadism, by reviewing data derived from both human and animal studies. The prevalence of NAFLD is high in men with hypogonadism, including those with idiopathic hypogonadotropic hypogonadism (IHH), as well as in women in post- menopause, those under estrogen receptor antagonist treatment or women with Turner syndrome...
November 23, 2016: Minerva Endocrinologica
https://www.readbyqxmd.com/read/27862257/regulation-of-hedgehog-signaling-in-chicken-embryonic-stem-cells-differentiation-into-male-germ-cells-gallus
#17
Hao Chen, Qisheng Zuo, Yinjie Wang, Mahmoud F Ahmed, Kai Jin, Jiuzhou Song, Yani Zhang, Bichun Li
The study aims to analyze the key signaling pathways in regulating the process of embryonic stem cells (ESCs) differentiation into spermatogonial stem cells (SSCs). Based on RNA Sequencing result, we further explored the specific regulating mechanisms of Hedgehog (HH) signaling in this process. HH signaling was found to be a crucial signaling pathway participating in the differentiation process of ESCs to SSCs. In Retinoic acid (RA) induced in vitro differentiation assay, the expression of two germ cell marker genes, integrin α6, and integrin β1, was observed to significantly increase, while it decreased dramatically when IHH was knocked down...
November 15, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27802423/transfection-of-the-ihh-gene-into-rabbit-bmscs-in-a-simulated-microgravity-environment-promotes-chondrogenic-differentisearchation-and-inhibits-cartilage-aging
#18
Peng-Cheng Liu, Kuan Liu, Jun-Feng Liu, Kuo Xia, Li-Yang Chen, Xing Wu
The effect of overexpressing the Indian hedgehog (IHH) gene on the chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) was investigated in a simulated microgravity environment. An adenovirus plasmid encoding the rabbit IHH gene was constructed in vitro and transfected into rabbit BMSCs. Two large groups were used: conventional cell culture and induction model group and simulated microgravity environment group. Each large group was further divided into blank control group, GFP transfection group, and IHH transfection group...
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27801732/wif-1-and-ihh-expression-and-clinical-significance-in-patients-with-lung-squamous-cell-carcinoma-and-adenocarcinoma
#19
Yue Zhang, Chunhong Hu
This study investigated the expression of wingless-type inhibitory factor-1 (WIF-1) and Ihh protein in tumor tissues and their clinical significance in patients with lung squamous cell carcinoma and adenocarcinoma. The expression of WIF-1 and Ihh protein in 74 squamous cell carcinomas and 76 adenocarcinomas was measured by immunohistochemistry. The percentage of positive WIF-1 protein expression was significantly higher, while positive Ihh protein expression was significantly lower in patients with well-differentiated lung squamous cell carcinoma and adenocarcinoma, tumor node metastasis (TNM) stage I disease, and lymph node metastasis than that in patients with poorly differentiated tumor, TNM stage III disease, and lymph node metastasis (P<0...
October 31, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27784237/the-roles-of-endoplasmic-reticulum-stress-in-the-pathophysiological-development-of-cartilage-and-chondrocytes
#20
Xiaoliang Yuan, Haiqing Liu, Linfu Li, Hai Liu, Jianqiong Yang, Weimei Shi, Longhuo Wu
Endoplasmic reticulum (ER) has evolved an adaptive mechanism called unfolded protein response (UPR) at the initial stage to restore cellular homeostasis. The three ER transmembrane sensors, including IRE1α, PERK, and ATF6 are the key factors to decide cell fates. They exhibit both advantageous and disadvantageous effects, which depending on the micro-environmental state of cells. ER stress has been implicated in chondrocytes proliferation, differentiation, and hypertrophy through regulating transcriptional factors SOX9, Ihh, BMP-2, RUNX, and HIF1/2α...
October 25, 2016: Current Pharmaceutical Design
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