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Weiguang Wang, Buer Song, Teni Anbarchian, Anna Shirazyan, Joshua E Sadik, Karen M Lyons
TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO), global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes...
October 2016: PLoS Genetics
Tao Wang, Xinping Zhang, Daniel D Bikle
5-10% of fractures fail to heal normally leading to additional surgery, morbidity, and altered quality of life. Fracture healing involves the coordinated action of stem cells primarily coming from the periosteum which differentiate into the chondrocytes and osteoblasts, forming first the soft (cartilage) callus followed by the hard (bone) callus. These stem cells are accompanied by a vascular invasion that appears critical for the differentiation process and which may enable the entry of osteoclasts necessary for the remodeling of the callus into mature bone...
October 12, 2016: Journal of Cellular Physiology
Xuan Wen, Xiaogang Li, Yubing Tang, Junzhou Tang, Siru Zhou, Yangli Xie, Jingyuan Guo, Jing Yang, Xiaolan Du, Nan Su, Lin Chen
Chondrogenesis can regulate bone formation. Fibroblast growth factor receptor 3, highly expressed in chondrocytes, is a negative regulator of bone growth. To investigate whether chondrocyte FGFR3 regulates osteogenesis, thereby contributing to postnatal bone formation and bone remodeling, mice with conditional knockout of Fgfr3 in chondrocytes (mutant, MUT) were generated. MUT mice displayed overgrowth of bone with lengthened growth plates. Bone mass of MUT mice was significantly increased at both 1 and 4 months of age...
October 11, 2016: Journal of Biological Chemistry
Zhibin Wang, Wei Li, Chun Li, Yang Yang, Wang Li, Liying Zhang, Shumei Sun, Junxiang Li, Yidong Cai
The present study aimed to investigate the expression levels of components of the Hedgehog signaling pathway (HH) during the proliferation of a liver stem cell subgroup, namely small hepatocyte-like progenitor cells (SHPCs). Retrorsine-treated Fisher 344 rats underwent a partial hepatectomy (PH) to induce the proliferation of SHPCs, after which reverse transcription-polymerase chain reaction (PCR), quantitative PCR, immunohistochemistry and western blot analysis were performed to analyze the expression of various components of the HH in primary SHPCs at different times points post-PH...
October 2016: Experimental and Therapeutic Medicine
Antonis Dagklis, Sofie Demeyer, Jolien De Bie, Enrico Radaelli, Daphnie Pauwels, Sandrine Degryse, Olga Gielen, Carmen Vicente, Roel Vandepoel, Ellen Geerdens, Anne Uyttebroeck, Nancy Boeckx, Charles E de Bock, Jan Cools
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive childhood leukemia that is caused by the accumulation of multiple genomic lesions resulting in transcriptional deregulation and increased cell proliferation and survival. Through analysis of gene expression data, we provide evidence that the hedgehog pathway is activated in 20% of T-ALL samples. Hedgehog pathway activation is associated with ectopic expression of the hedgehog ligands SHH or IHH, and with upregulation of the transcription factor GLI1...
September 30, 2016: Blood
Matthias Kamper, Mats Paulsson, Frank Zaucke
Collagen IX (Col IX) is a component of the cartilage extracellular matrix and contributes to its structural integrity. Polymorphisms in the genes encoding the Col IX ɑ2- and ɑ3-chains are associated with early onset of disc degeneration. Col IX-deficient mice already display changes in the spine at the newborn stage and premature disc degeneration starting at 6 months of age. To determine the role of Col IX in early spine development and to identify molecular mechanisms underlying disc degeneration, the embryonic development of the spine was analyzed in Col IX -/- mice...
September 25, 2016: Cell and Tissue Research
Ting Xu, Gaoli Xu, Zhiyuan Gu, Huiling Wu
OBJECTIVE: The aim of this study was to investigate the changes in hedgehog (Hh) expression and its possible effects on cartilage degeneration in adjuvant-induced temporomandibular joint osteoarthritis (TMJOA) of rats. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into experimental osteoarthritis (OA) and sham control groups. The bilateral TMJs of six rats from each group were harvested at three, seven, 14, and 28 days. Histological changes in condylar cartilage were assessed by hematoxylin and eosin, toluidine blue, and safranin O staining...
September 20, 2016: Journal of Oral Pathology & Medicine
Yikui Tian, Dongfeng Pan, Mahendra D Chordia, Brent A French, Irving L Kron, Zequan Yang
The spleen plays a critical role in post-infarct myocardial remodeling. However, the role of the spleen in exacerbating myocardial infarction (MI) during acute ischemia/reperfusion (I/R) injury is unknown. The present study tests the hypothesis that splenic leukocytes are activated by substances released from ischemic myocardium to subsequently exacerbate myocardial injury during reperfusion. The left coronary artery in C57BL/6 mice underwent various durations of occlusion followed by 60 min of reperfusion (denoted as min/min of I/R) with or without splenectomy prior to I/R injury...
November 2016: Basic Research in Cardiology
Chen Yao, Gang Li, Yeyong Qian, Ming Cai, Hong Yin, Li Xiao, Wei Tang, Fengjie Guo, Bingyi Shi
To investigate the effect of pentoxifylline (PTX) on spermatogenesis dysfunction induced by intermittent hypobaric hypoxia (IHH) and unveil the underlying mechanism, experimental animals were assigned to Control, IHH+Vehicle, and IHH+PTX groups and exposed to 4 cycles of 96 h of hypobaric hypoxia followed by 96 h of normobaric normoxia for 32 days. PTX was administered for 32 days. Blood and tissue samples were collected 7 days thereafter. Serum malondialdehyde levels were used to assess lipid peroxidation; ferric-reducing antioxidant power (FRAP), superoxide dismutase, and catalase and glutathione peroxidase enzyme activities were assessed to determine antioxidant capacity in various samples...
2016: Oxidative Medicine and Cellular Longevity
Yan Jiang, Jiahong Chen, Cong Yue, Hang Zhang, Tao Chen
Trichloroethylene (TCE), a common environmental contaminant, causes hepatocellular carcinoma in mice but not in rats. To understand the mechanisms of the species-specific hepatocarcinogenecity of TCE, we examined the methylation status of DNA in the liver of rats exposed to TCE at 0 or 1000 mg/kg b.w. for 5 days using MeDIP-chip, bisulfite sequencing, COBRA, and LC-MS/MS. The related mRNA expression levels were measured by qPCR. Although no global DNA methylation change was detected, 806 genes were hypermethylated and 186 genes were hypomethylated...
October 17, 2016: Chemical Research in Toxicology
Hasan Öztin, Eylem Çağıltay, Sinan Çağlayan, Mustafa Kaplan, Yaşam Kemal Akpak, Nilay Karaca, Mesut Tığlıoğlu
Male hypogonadism is defined as the deficiency of testosterone or sperm production synthesized by testicles or the deficiency of both. The reasons for hypogonadism may be primary, meaning testicular or secondary, meaning hypothalamohypophyseal. In hypogonadotropic hypogonadism (HH), there is indeficiency in gonadotropic hormones due to hypothalamic or hypophyseal reasons. Gonadotropin-releasing hormone (GnRH) is an important stimulant in releasing follicular stimulant hormone (FSH), mainly luteinizing hormone (LH)...
September 10, 2016: Gynecological Endocrinology
Rajeev Chaudhary, Ming-Song Lee, Kuwabo Mubyana, Sarah Duenwald-Kuehl, Lyndsey Johnson, Jarred Kaiser, Ray Vanderby, Kevin W Eliceiri, David T Corr, Matthew S Chin, Wan-Ju Li, Paul J Campagnola, Matthew A Halanski
PURPOSE: The accepted mechanism explaining the accelerated growth following periosteal resection is that the periosteum serves as a mechanical restraint to restrict physeal growth. To test the veracity of this mechanism we first utilized Second Harmonic Generation (SHG) imaging to measure differences of periosteal fiber alignment at various strains. Additionally, we measured changes in periosteal growth factor transcription. Next we utilized SHG imaging to assess the alignment of the periosteal fibers on the bone both before and after periosteal resection...
November 2016: Bone
Maria Gnarra, Gerald Behr, Alison Kitajewski, June K Wu, Sudha A Anupindi, Carrie J Shawber, Nick Zavras, Dimitrios Schizas, Chris Salakos, Konstantinos P Economopoulos
We aim to provide an up-to-date summary of infantile hepatic hemangioma (IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver. Eligible peer-reviewed articles on hepatic infantile hemangiomas, published between 2000 and 2015, were reviewed for this study. IHH is the most common hepatic vascular tumor in children. Once a liver mass is identified in an infant, the differential diagnosis ranges from vascular malformations to benign and malignant tumors including mesenchymal hamartoma, hepatoblastoma, metastatic neuroblastoma, so careful physical examination, imaging studies, and, if indicated, tumor markers and biopsy, are of pivotal importance to ascertain the correct diagnosis...
August 8, 2016: World Journal of Clinical Pediatrics
B Mohelnikova-Duchonova, M Kocik, B Duchonova, V Brynychova, M Oliverius, J Hlavsa, E Honsova, J Mazanec, Z Kala, I Ojima, D J Hughes, J E Doherty, H A Murray, M A Crockard, R Lemstrova, P Soucek
The Hedgehog pathway is one of the major driver pathways in pancreatic ductal adenocarcinoma. This study investigated prognostic importance of Hedgehog signaling pathway in pancreatic cancer patients who underwent a radical resection. Tumors and adjacent non-neoplastic pancreatic tissues were obtained from 45 patients with histologically verified pancreatic cancer. The effect of experimental taxane chemotherapy on the expression of Hedgehog pathway was evaluated in vivo using a mouse xenograft model prepared using pancreatic cancer cell line Paca-44...
August 30, 2016: Pharmacogenomics Journal
Jennifer Fischer, Marlen Ortel, Sebastien Hagmann, Andreas Hoeflich, Wiltrud Richter
Generation of phenotypically stable, articular chondrocytes from mesenchymal stromal cells (MSCs) is still an unaccomplished task, with formation of abundant, hyaline extracellular matrix, and avoidance of hypertrophy being prime challenges. We recently demonstrated that parathyroid hormone-related protein (PTHrP) is a promising factor to direct chondrogenesis of MSCs towards an articular phenotype, since intermittent PTHrP application stimulated cartilage matrix production and reduced undesired hypertrophy...
December 2016: Journal of Cellular Physiology
Mary R Richards, Lacey Plummer, Yee-Ming Chan, Margaret F Lippincott, Richard Quinton, Philip Kumanov, Stephanie B Seminara
BACKGROUND: A constellation of neurodegenerative disorders exists (Gordon Holmes syndrome, 4H leucodystrophy, Boucher-Neuhauser syndrome) in which patients suffer from both neurological disease (typically manifested by ataxia) and reproductive failure (idiopathic hypogonadotropic hypogonadism (IHH)). POLR3B, which encodes the second largest subunit of RNA polymerase III (pol III), and POLR3A, which forms the pol III catalytic centre, are associated with 4H leucodystrophy. METHODS: Whole exome sequencing was performed on a large cohort of subjects with IHH (n=565)...
August 10, 2016: Journal of Medical Genetics
Lomeli R Carpio, Elizabeth W Bradley, Meghan E McGee-Lawrence, Megan M Weivoda, Daniel D Poston, Amel Dudakovic, Ming Xu, Tamar Tchkonia, James L Kirkland, Andre J van Wijnen, Merry Jo Oursler, Jennifer J Westendorf
Histone deacetylase (HDAC) inhibitors are efficacious epigenetic-based therapies for some cancers and neurological disorders; however, each of these drugs inhibits multiple HDACs and has detrimental effects on the skeleton. To better understand how HDAC inhibitors affect endochondral bone formation, we conditionally deleted one of their targets, Hdac3, pre- and postnatally in type II collagen α1 (Col2α1)-expressing chondrocytes. Embryonic deletion was lethal, but postnatal deletion of Hdac3 delayed secondary ossification center formation, altered maturation of growth plate chondrocytes, and increased osteoclast activity in the primary spongiosa...
2016: Science Signaling
Michael S Hildebrand, Nicole G Griffin, John A Damiano, Elisa J Cops, Rosemary Burgess, Ezgi Ozturk, Nigel C Jones, Richard J Leventer, Jeremy L Freeman, A Simon Harvey, Lynette G Sadleir, Ingrid E Scheffer, Heather Major, Benjamin W Darbro, Andrew S Allen, David B Goldstein, John F Kerrigan, Samuel F Berkovic, Erin L Heinzen
Hypothalamic hamartoma (HH) with gelastic epilepsy is a well-recognized drug-resistant epilepsy syndrome of early life.(1) Surgical resection allows limited access to the small deep-seated lesions that cause the disease. Here, we report the results of a search for somatic mutations in paired hamartoma- and leukocyte-derived DNA samples from 38 individuals which we conducted by using whole-exome sequencing (WES), chromosomal microarray (CMA), and targeted resequencing (TRS) of candidate genes. Somatic mutations were identified in genes involving regulation of the sonic hedgehog (Shh) pathway in 14/38 individuals (37%)...
August 4, 2016: American Journal of Human Genetics
Sihua Jin, Feng Zhu, Yanyun Wang, Guoqiang Yi, Junying Li, Ling Lian, Jiangxia Zheng, Guiyun Xu, Rengang Jiao, Yu Gong, Zhuocheng Hou, Ning Yang
The Creeper trait, a classical monogenic phenotype of chicken, is controlled by a dominant semi-lethal gene. This trait has been widely cited in the genetics and molecular biology textbooks for illustrating autosomal dominant semi-lethal inheritance over decades. However, the genetic basis of the Creeper trait remains unknown. Here we have utilized ultra-deep sequencing and extensive analysis for targeting causative mutation controlling the Creeper trait. Our results indicated that the deletion of Indian hedgehog (IHH) gene was only found in the whole-genome sequencing data of lethal embryos and Creeper chickens...
2016: Scientific Reports
Leilei Zhong, Xiaobin Huang, Marcel Karperien, Janine N Post
Osteoarthritis (OA) is a multifactorial disease characterized by gradual degradation of joint cartilage. This study aimed to quantify major pathogenetic factors during OA progression in human cartilage. Cartilage specimens were isolated from OA patients and scored 0-5 according to the Osteoarthritis Research Society International (OARSI) guidelines. Protein and gene expressions were measured by immunohistochemistry and qPCR, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to detect apoptotic cells...
2016: International Journal of Molecular Sciences
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