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| 1 | Osteoblasts are inherently programmed to repel sensory innervation显示文摘Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development.Yet,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited.Here,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells crosstalk.The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression.We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB differentiation.We noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal repulsion.Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons.Finally,to strengthen our model,we localized the expression of Shh by osteoblasts in bone tissue.Overall,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation. | Luis Leitao Estrela Neto Francisco Conceicao Ana Monteiro Marina Couto Cecilia JAlves Daniela MSousa Meriem Lamghari | 2020 | Bone Research2020，8，3： | 4 |
| 2 | TRAIL induces apoptosis in human colorectal adenoma cell lines and human colorectal adenomas 显示文摘 | Jalving M de Jong S Koornstra JJ | 2006 | Clin Cancer Res2006，12，141： | 1 |
| 3 | Characterization of the Kexin-Iike maturase of Asper?gillus niger显示文摘 | JALVING R VAN DE VONDERVOORT PJ VISSERJ | 2000 | Appl Environ Microbiol2000，66，1： | 1 |
| 4 | In-creased risk of fundic gland polyps during long-term protonpump inhibitor therapy 显示文摘 | JALVING M KOORNSTRA JJ WESSELING J | 2006 | Aliment Pharmacol Ther2006，24，9： | 1 |
| 5 | Metformin: Taking away the candy for cancer?显示文摘 | Jalving M Gietema JA Lefrandt JD | 2010 | Eur J Cancer2010，46，： | 1 |
| 6 | Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy 显示文摘 | Jalving M Koomstra JJ Wesseling J | 2006 | Aliment Pharmacol Ther2006，24，9： | 1 |
| 7 | Chicken single nucleotide polymorphism identification and selection for genetic mapping显示文摘 | Jalving R Slot R Oost B A | 2004 | Poultry Science2004，83，： | 1 |
| 8 | Mefformin : taking away the candy for cancer? 显示文摘 | Jalving M Gietema JA Lefrandt JD | 2010 | Eur J Can2010，46，13： | 1 |
| 9 | A Toolbox of Aiding Techniques for the HUGIN AUV Integrated Inertial Navigation System显示文摘 | Jalving B Gade K Hagen O K | | 0，，03： | 1 |
| 10 | Incr- eased risk of fundic gland polyps during long-term proton pump inhibitor therapy 显示文摘 | JALVING M KOORNSTRA J J WESSELING J | 2006 | Aliment Pharmacol Ther2006，24，9： | 1 |
| 11 | Integrated camera-based navigation 显示文摘 | HAFSKJOLD B H JALVING B HAGEN P E | 2000 | The Journal of Naviga- tion2000，53，2： | 1 |
| 12 | Metformin: Taking away the candy for cancer?显示文摘 | Mathilde Jalving Jourik A. Gietema Joop D. Lefrandt Steven de Jong Anna K.L. Reyners Rijk O.B. Gans Elisabeth G.E. de Vries | 2010 | European Journal of Cancer2010，，13： | 1 |
| 13 | Increased risk of fundic gland polyps during long -term proton pump inhibitor therapy显示文摘 | Jalving M Koornstra J J Wesseling J | 2006 | Aliment Pharmacol Ther2006，24，： | 1 |
| 14 | DVL velocity aiding in the HUGIN 1000 intergrated inertial navigation system 显示文摘 | Jalving B Gade K Svartveit K | 2004 | Model- ing Identification and Control2004，24，4： | 1 |
| 15 | Metformin:taking away the candy for cancer?显示文摘 | Jalving M Gietema JA Lefrandt JD | 2010 | Eur J Cancer2010，46，13： | 1 |
| 16 | The NDRE-AUV flight control system显示文摘 | JALVING B | 1994 | IEEE Journal of Oceanic Engineering1994，19，4： | 1 |
| 17 | Independent induction of caspase-8 and cFLIP expression during colorectal carcinogenesis in sporadic and HNPCC adenomas and carcinomas显示文摘 | Heijink DM Kleibeuker JH Jalving M | | 0，，05： | 1 |
| 18 | Metformin: taking away the candy for cancer? 显示文摘 | Jalving M Gietema JA Lefrandt JD | 2010 | Eur J Cancer2010，46，13： | 1 |
| 19 | The NDRE-AUV flight control system显示文摘 | Bjern Jalving | 1994 | lEEE Journal of Ocean Engineering1994，，19： | 1 |
| 20 | A toolbox of aiding techniques for the HUGIN AUV integrated inertial naviga- tion system显示文摘 | JALVING B GADE K HAGEN O K | 2003 | Oceans2003，9，： | 1 |
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