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https://www.readbyqxmd.com/read/29089388/the-flavonol-glycoside-icariin-promotes-bone-formation-in-growing-rats-by-activating-the-camp-signaling-pathway-in-primary-cilia-of-osteoblasts
#1
Wengui Shi, Yuhai Gao, Yuanyuan Wang, Jian Zhou, Zhenlong Wei, Xiaoni Ma, Huiping Ma, Cory J Xian, Jufang Wang, Keming Chen
Icariin, a prenylated flavonol glycoside isolated from the herb Epimedium, has been considered as a potential alternative therapy for osteoporosis. Previous research has shown that unlike other flavonoids, icariin is unlikely to act via the estrogen receptor, but its exact mechanism of action is unknown. In this study, using rat calvarial osteoblast culture and rat bone growth models, we demonstrated that icariin promotes bone formation by activating the cAMP/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway requiring functional primary cilia of osteoblasts...
October 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29089384/the-guanine-nucleotide-exchange-factor-arf-like-protein-13b-is-essential-for-assembly-of-the-mouse-photoreceptor-transition-zone-and-outer-segment
#2
Christin Hanke-Gogokhia, Zhijian Wu, Ali Sharif, Hussein Yazigi, Jeanne M Frederick, Wolfgang Baehr
ARL13b is a small GTPase that functions as a guanosine nucleotide exchange factor (GEF) for ARL3-GDP. ARL13b is located exclusively in photoreceptor outer segments (OS) presumably anchored to discs by palmitoylation, whereas ARL3 is an inner segment cytoplasmic protein. Hypomorphic mutations affecting the ARL13b G‑domain inactivate GEF activity and lead to Joubert Syndrome (JS) in human. However, the molecular mechanisms in ARL13b mutation-induced JS, particularly the function of primary cilia, are still incompletely understood...
October 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29066540/tgf-%C3%AE-receptor-i-ii-trafficking-and-signaling-at-primary-cilia-are-inhibited-by-ceramide-to-attenuate-cell-migration-and-tumor-metastasis
#3
Salih Gencer, Natalia Oleinik, Jisun Kim, Shanmugam Panneer Selvam, Ryan De Palma, Mohammed Dany, Rose Nganga, Raquela J Thomas, Can E Senkal, Philip H Howe, Besim Ogretmen
Signaling by the transforming growth factor-β (TGF-β) receptors I and II (TβRI/II) and the primary cilia-localized sonic hedgehog (Shh) pathway promote cell migration and, consequently, tumor metastasis. In contrast, the sphingolipid ceramide inhibits cell proliferation and tumor metastasis. We investigated whether ceramide metabolism inhibited TβRI/II trafficking to primary cilia to attenuate cross-talk between TβRI/II and the Shh pathway. We found that ceramide synthase 4 (CerS4)-generated ceramide stabilized the association between TβRI and the inhibitory factor Smad7, which limited the trafficking of TβRI/II to primary cilia...
October 24, 2017: Science Signaling
https://www.readbyqxmd.com/read/29061117/diatom-flagellar-genes-and-their-expression-during-sexual-reproduction-in-leptocylindrus-danicus
#4
Deepak Nanjappa, Remo Sanges, Maria I Ferrante, Adriana Zingone
BACKGROUND: Flagella have been lost in the vegetative phase of the diatom life cycle, but they are still present in male gametes of centric species, thereby representing a hallmark of sexual reproduction. This process, besides maintaining and creating new genetic diversity, in diatoms is also fundamental to restore the maximum cell size following its reduction during vegetative division. Nevertheless, sexual reproduction has been demonstrated in a limited number of diatom species, while our understanding of its different phases and of their genetic control is scarce...
October 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28981158/low-intensity-pulsed-ultrasound-stimulation-promotes-osteoblast-differentiation-through-hedgehog-signaling
#5
Kenichi Matsumoto, Tsuyoshi Shimo, Naito Kurio, Tatsuo Okui, Soichiro Ibaragi, Yuki Kunisada, Kyoichi Obata, Masanori Masui, Pang Pai, Yuu Horikiri, Nobuyuki Yamanaka, Masaharu Takigawa, Akira Sasaki
Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group...
October 5, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28954202/ciliopathy-protein-tmem107-plays-multiple-roles-in-craniofacial-development
#6
P Cela, M Hampl, N A Shylo, K J Christopher, M Kavkova, M Landova, T Zikmund, S D Weatherbee, J Kaiser, M Buchtova
A broad spectrum of human diseases called ciliopathies is caused by defective primary cilia morphology or signal transduction. The primary cilium is a solitary organelle that responds to mechanical and chemical stimuli from extracellular and intracellular environments. Transmembrane protein 107 (TMEM107) is localized in the primary cilium and is enriched at the transition zone where it acts to regulate protein content of the cilium. Mutations in TMEM107 were previously connected with oral-facial-digital syndrome, Meckel-Gruber syndrome, and Joubert syndrome exhibiting a range of ciliopathic defects...
September 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28901584/the-primary-cilium-as-a-signaling-nexus-for-growth-plate-function-and-subsequent-skeletal-development
#7
REVIEW
Emily R Moore, Christopher R Jacobs
The primary cilium is a solitary, antenna-like sensory organelle with many important roles in cartilage and bone development, maintenance, and function. The primary cilium's potential role as a signaling nexus in the growth plate makes it an attractive therapeutic target for diseases and disorders associated with bone development and maintenance. Many signaling pathways that are mediated by the cilium - such as Hh, Wnt, Ihh/PTHrP, TGFβ, BMP, FGF, and Notch - are also known to influence endochondral ossification, primarily by directing growth plate formation and chondrocyte behavior...
September 13, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28901443/basic-fibroblast-growth-factor-increases-ift88-expression-in-chondrocytes
#8
Daolu Zhan, Wei Xiang, Fengjing Guo, Yuanzheng Ma
Intraflagellar transport protein 88 (IFT88) is protein crucial for the assembly and maintenance of primary cilia in chondrocytes. Primary cilia regulate mechanical and chemical signals in chondrocytes; however, the effects of cytokines on IFT88 expression and cilia formation and maintenance remain to be elucidated. Therefore, the role of basic fibroblast growth factor (bFGF) on IFT88 expression were examined in theATDC5 murine chondrocytic line, in order to investigate the signaling pathways involved in this process...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900213/copine-7-binds-to-the-cell-surface-receptor-nucleolin-and-regulates-ciliogenesis-and-dspp-expression-during-odontoblast-differentiation
#9
You-Mi Seo, Su-Jin Park, Hye-Kyung Lee, Joo-Cheol Park
Tooth development is a progressive process regulated by interactions between epithelial and mesenchymal tissues. Our previous studies showed that copine-7 (Cpne7), a dental epithelium-derived protein, is a signalling molecule that is secreted by preameloblasts and regulates the differentiation of preodontoblasts into odontoblasts. However, the mechanisms involved in the translocation of Cpne7 from preameloblasts to preodontoblasts and the functions of Cpne7 during odontogenesis are poorly understood. Here, we showed that the internalization of Cpne7 was mediated primarily by caveolae...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706295/dgk%C3%AE-triggers-endoplasmic-reticulum-release-of-ift88-containing-vesicles-destined-for-the-assembly-of-primary-cilia
#10
Jie Ding, Lei Shao, Yixing Yao, Xin Tong, Huaize Liu, Shen Yue, Lu Xie, Steven Y Cheng
The morphogenic factor Sonic hedgehog (Shh) signals through the primary cilium, which relies on intraflagellar transport to maintain its structural integrity and function. However, the process by which protein and lipid cargos are delivered to the primary cilium from their sites of synthesis still remains poorly characterized. Here, we report that diacylglycerol kinase δ (DGKδ), a residential lipid kinase in the endoplasmic reticulum, triggers the release of IFT88-containing vesicles from the ER exit sites (ERES), thereby setting forth their movement to the primary cilium...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28671279/impairment-of-primary-cilia-contributes-to-visceral-adiposity-of-high-fat-diet-fed-mice
#11
Ni Qiu, Wei-Jin Fang, Hong-Sheng Li, Zhi-Min He, Zhou-Sheng Xiao, Yan Xiong
Deficiency of primary cilia formation by knockout kinesin family member 3A (Kif3a) in mature osteoblasts led to osteopenia and enhanced adipogenesis. Adipogenesis plays an important role in adipose tissue expansion by High-fat-diet (HFD) induced obesity. Whether primary cilia participate in high-fat-diet induced adiposity remains unclear. In this study, we found that the number and length of primary cilia and expression levels of KIF3A and intraflagellar transport 88 homolog (IFT88) mRNA and proteins reached peak on the day 3 of adipogenesis, followed by a decrease to reach low basal expression levels at day 9 when differentiated to lipid accumulating adipocytes in VAT-SVFs derived from lean mice...
July 3, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28607127/role-of-the-primary-cilia-on-the-macula-densa-and-thick-ascending-limbs-in-regulation-of-sodium-excretion-and-hemodynamics
#12
Jiangping Song, Lei Wang, Fan Fan, Jin Wei, Jie Zhang, Yan Lu, Yiling Fu, Shaohui Wang, Luis A Juncos, Ruisheng Liu
We investigated the significance of the primary cilia on the macula densa and thick ascending limb (TAL) in regulation of renal hemodynamics, sodium excretion, and blood pressure in this study. A tissue-specific primary cilia knock-out (KO) mouse line was generated by crossing NKCC2-Cre mice with IFT88-Δ/flox mice (NKCC2(CRE); IFT88Δ(/flox)), in which the primary cilia were deleted from the macula densa and TAL. NO generation was measured with a fluorescent dye (4,5-diaminofluorescein diacetate) in isolated perfused juxtaglomerular apparatus...
August 2017: Hypertension
https://www.readbyqxmd.com/read/28586053/hdac6-inhibition-suppresses-chondrosarcoma-by-restoring-the-expression-of-primary-cilia
#13
Wei Xiang, Fengjing Guo, Weiting Cheng, Jiaming Zhang, Junming Huang, Rui Wang, Zhongxi Ma, Kai Xu
Chondrosarcoma is a bone tumor characterized by the secretion of a cartilage-like extracellular matrix. It has been proved to lack extracellular sensor primary cilia. This study aimed to illustrate a feasible therapeutic method for chondrosarcoma by regulating primary cilia assembly through inhibiting histone deacetylases 6 (HDAC6) activation. In order to detect the interaction between primary cilia and HDAC6 in human chondrosarcoma, Tubastatin A and small interfering RNA (siRNA) were used to inhibit the endogenous expression of HDAC6...
June 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28556366/a-role-for-primary-cilia-in-aortic-valve-development-and-disease
#14
Katelynn A Toomer, Diana Fulmer, Lilong Guo, Alex Drohan, Neal Peterson, Paige Swanson, Brittany Brooks, Rupak Mukherjee, Simon Body, Joshua H Lipschutz, Andy Wessels, Russell A Norris
BACKGROUND: Bicuspid aortic valve (BAV) disease is the most common congenital heart defect, affecting 0.5-1.2% of the population and causing significant morbidity and mortality. Only a few genes have been identified in pedigrees, and no single gene model explains BAV inheritance, thus supporting a complex genetic network of interacting genes. However, patients with rare syndromic diseases that stem from alterations in the structure and function of primary cilia ("ciliopathies") exhibit BAV as a frequent cardiovascular finding, suggesting primary cilia may factor broadly in disease etiology...
August 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28500304/microgravity-induces-inhibition-of-osteoblastic-differentiation-and-mineralization-through-abrogating-primary-cilia
#15
Wengui Shi, Yanfang Xie, Jinpeng He, Jian Zhou, Yuhai Gao, Wenjun Wei, Nan Ding, Huiping Ma, Cory J Xian, Keming Chen, Jufang Wang
It is well documented that microgravity in space environment leads to bone loss in astronauts. These physiological changes have also been validated by human and animal studies and modeled in cell-based analogs. However, the underlying mechanisms are elusive. In the current study, we identified a novel phenomenon that primary cilia (key sensors and functioning organelles) of rat calvarial osteoblasts (ROBs) gradually shrank and disappeared almost completely after exposure to simulated microgravity generated by a random positioning machine (RPM)...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28489570/transcriptome-profiling-identifies-a-recurrent-cryl1-ift88-chimeric-transcript-in-hepatocellular-carcinoma
#16
Yi Huang, Jiaying Zheng, Dunyan Chen, Feng Li, Wenbing Wu, Xiaoli Huang, Yanan Wu, Yangyang Deng, Funan Qiu
We performed transcriptome sequencing for hepatocellular carcinoma (HCC) and adjacent non-tumorous tissues to investigate the molecular basis of HCC. Nine HCC patients were recruited and differentially expressed genes (DEGs) were identified. Candidate fusion transcripts were also identified. A total of 1943 DEGs were detected, including 690 up-regulated and 1253 down-regulated genes, and enriched in ten pathways including cell cycle, DNA replication, p53, complement and coagulation cascades, etc. Seven candidate fusion genes were detected and CRYL1-IFT88 was successfully validated in the discovery sequencing sample and another 5 tumor samples with the recurrent rate of about 9...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468945/primary-cilia-control-the-maturation-of-tubular-lumen-in-renal-collecting-duct-epithelium
#17
Thomas Ernandez, Olga Komarynets, Alexandra Chassot, Soushma Sougoumarin, Priscilla Soulié, Yubao Wang, Roberto Montesano, Eric Feraille
The key role of the primary cilium in developmental processes is illustrated by ciliopathies resulting from genetic defects of its components. Ciliopathies include a large variety of dysmorphic syndromes that share in common the presence of multiple kidney cysts. These observations suggest that primary cilia may control morphogenetic processes in the developing kidney. In this study, we assessed the role of primary cilium in branching tubulogenesis and/or lumen development using kidney collecting duct-derived mCCDN21 cells that display spontaneous tubulogenic properties when grown in collagen-Matrigel matrix...
July 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28352462/fixation-methods-can-differentially-affect-ciliary-protein-immunolabeling
#18
Kiet Hua, Russell J Ferland
BACKGROUND: Primary cilia are immotile, microtubule-based organelles present on most cells. Defects in primary cilia presence/function result in a category of developmental diseases referred to as ciliopathies. As the cilia field progresses, there is a need to consider both the ciliary and extraciliary roles of cilia proteins. However, traditional fixation methods are not always suitable for examining the full range of localizations of cilia proteins. Here, we tested a variety of fixation methods with commonly used cilia markers to determine the most appropriate fixation method for different cilia proteins...
2017: Cilia
https://www.readbyqxmd.com/read/28346501/a-tissue-specific-role-for-intraflagellar-transport-genes-during-craniofacial-development
#19
Elizabeth N Schock, Jaime N Struve, Ching-Fang Chang, Trevor J Williams, John Snedeker, Aria C Attia, Rolf W Stottmann, Samantha A Brugmann
Primary cilia are nearly ubiquitous, cellular projections that function to transduce molecular signals during development. Loss of functional primary cilia has a particularly profound effect on the developing craniofacial complex, causing several anomalies including craniosynostosis, micrognathia, midfacial dysplasia, cleft lip/palate and oral/dental defects. Development of the craniofacial complex is an intricate process that requires interactions between several different tissues including neural crest cells, neuroectoderm and surface ectoderm...
2017: PloS One
https://www.readbyqxmd.com/read/28302912/intraflagellar-transport-protein-ift52-recruits-ift46-to-the-basal-body-and-flagella
#20
Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, Kaiyao Huang
Cilia are microtubule-based organelles and perform motile, sensing and signaling functions. The assembly and maintenance of cilia depend on intraflagellar transport (IFT). Besides ciliary localization, most IFT proteins accumulate at basal bodies. However, little is known about the molecular mechanism of basal body targeting of IFT proteins. We first identified the possible basal body-targeting sequence in IFT46 by expressing IFT46 truncation constructs in an ift46-1 mutant. The C-terminal sequence between residues 246-321, termed BBTS3, was sufficient to target YFP to basal bodies in the ift46-1 strain...
May 1, 2017: Journal of Cell Science
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