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| 1 | Ciliary parathyroid hormone signaling activates transforming growth factor-βto maintain intervertebral disc homeostasis during aging显示文摘Degenerative disc disease(DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus(NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor(PTH1 R) to the cilia and enhances parathyroid hormone(PTH) signaling in NP cells. PTH induces transcription of integrin α_vβ_6 to activate the transforming growth factor(TGF)-β-connective tissue growth factor(CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH(iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1 R is expressed in both mouse and human NP cells. Importantly,knockout PTH1 R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1 R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD. | Liwei Zheng Yong Cao Shuangfei Ni Huabin Qi Zemin Ling Xin Xu Xuenong Zou Tianding Wu Ruoxian Deng Bo Hu Bo Gao Hao Chen Yusheng Li Jianxi Zhu Francis Tintani Shadpour Demehri Amit Jain Khaled M.Kebaish Shenghui Liao Cheryle A.Séguin Janet L.Crane Mei Wan Hongbin Lu Paul D.Sponseller Lee H.RileyIII Xuedong Zhou Jianzhong Hu Xu Cao | 2018 | Bone Research2018，6，3： | 13 |
| 2 | Establishment of a murine model of aggressive systemic mastocytosis/mast cell leukemia显示文摘 | DEMEHRI S CORBIN A LORIAUX M | 2006 | Exp Hematol2006，34，3： | 1 |
| 3 | Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity显示文摘 | Demehri S Liu Z Lee J | 2008 | PLoS Biol2008，6，5： | 1 |
| 4 | e8a2BCRABL:more frequent than other atypical BCR-ABL variants?显示文摘 | Demehri S Paschka P Schultheis B | 2005 | Leukemia2005，19，： | 1 |
| 5 | ATP- sensitive potassium channels mediate the anti-ischemic properties of ischemic and pharmacologic preconditioning in rat random- pattern skin flap显示文摘 | Beheshtian A Demehri S Kiumehr S | 2006 | Ann Plast Surg2006，57，： | 1 |
| 6 | ATP-sensitive potassium channels mediate the anti-ischemic properties of ischemic and pharmacologic preconditioning in rat random-pattern skin flap 显示文摘 | Beheshtian A Demehri S Kiumehr S | 2006 | Ann Plast Surg2006，57，1： | 1 |
| 7 | Epidermal Notchl loss promotes skin tumorigenesis by impacting the stromal microenvironment显示文摘 | Demehri S Turkoz A Kopan R | 2009 | Cancer Cell2009，16，： | 1 |
| 8 | Establishment of a murine model of aggressive systemic mastocytosis/mast cell leukemia显示文摘 | Demehri S Corbin A Loriaux M | 2006 | Exp Hematol2006，34，3： | 1 |
| 9 | Hirschsprung- associated enterocolitis : pathogenesis, treatment and prevention 显示文摘 | Demehri FR Halaweish IF Coran AG | 2013 | Pediatr Surg Int2013，29，： | 1 |
| 10 | Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP,a sentinel for epidermal integrity显示文摘 | Demehri S Liu Z Lee J | 2008 | PLoS Biol2008，6，5： | 1 |
| 11 | Volumetric quantification of type II endoleaks: An indicator for aneurysm sac growth following endovascular abdominal aortic aneurysm repair显示文摘 | Demehri S Signorelli J Kumamaru KK | 2014 | Radiology2014，271，1： | 1 |
| 12 | ATP-sensitive po-tassium channels mediate the anti-ischemic properties of ischemic and pharmacologic preconditioning in rat random-pattern skin flap显示文摘 | Beheshtian A Demehri S Kiumehr S | | 0，，01： | 1 |
| 13 | High sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients:correlation with clonal cytogenetic evolution but not response to therapy显示文摘 | Willis S Lange T Demehri S | 2005 | Blood2005，24，： | 1 |
| 14 | Axial and reformatted four-cham- ber right ventricle-to-left ventricle diameter ratios on pulmonary ct angiography as predictors of death after acute pulmonary embolism 显示文摘 | Lu MT Demehri S Cai T | 2012 | AJR Am J Roentgeno12012，198，6： | 1 |
| 15 | Image qual- ity improvement using an image-based noise reduction algorithm: initial experience in a phantom model for uri- nary stones显示文摘 | Demehri S Salazar P Steigner M L | 2012 | J Comput Assist Tomogr2012，36，5： | 1 |
| 16 | Intestinal epithelial cell ap- optosis and loss of barrier function in the setting of altered microhiota with enteral nutrient deprivation 显示文摘 | Demehri FR Barrett M Rails MW | 2013 | Front Cell Infect Microbiol2013，3，： | 1 |
| 17 | Quantification of urinarystone volume : attenuation threshold-based CT method-a technical note显示文摘 | Demehri S Kalra MK Rybicki FJ’ | 2011 | Radiology2011，258，3： | 1 |
| 18 | Elevated epidermal thymic stromal lymphopoietinlevels establish an antitumor environment in the skin显示文摘 | DEMEHRI S TURKOZ A MANIVASAGAM S etal | 2012 | Cancer Cell ?2012，22，： | 1 |
| 19 | Alpha 2-adrenoceptor and NO mediate the opioid subsensitivity in isolated tissues of cholestatic animals显示文摘 | DEMEHRI S SAMINI M NAMIRANIAN K | 2003 | Auton Autacoid Pharmacol2003，23，4： | 1 |
| 20 | Intestinal epithelial cellapoptosis and loss of barrier function in the setting of altered microbio-ta with enteral nutrient deprivation 显示文摘 | Demehri FH Barrett M Ralls MW | 2013 | Front Cell Infect Microbiol2013，3，： | 1 |
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