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| 1 | Inhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing显示文摘Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis,a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5(Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by si RNA, genetic deletion using the Cre-lox P system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing. | Mubashir Ahmad Benjamin Thilo Krüger Torsten Kroll Sabine Vettorazzi Ann-Kristin Dorn Florian Mengele Sooyeon Lee Sayantan Nandi Dilay Yilmaz Miriam Stolz Naveen Kumar Tangudu David Carro Vázquez Johanna Pachmayr Ion Cristian Cirstea Maja Vujic Spasic Aspasia Ploubidou Anita Ignatius Jan Tuckermann | 2022 | Bone Research2022,10,3: | 2 |
| 2 | Molecular mechanisms of glucocorticoids in the control of inflammation and lymphocyte apoptosis显示文摘 | Tuckermann JP Kleiman AM Pherson KG | 2005 | Crit Rev Clin Lab Sci2005,42,1: | 1 |
| 3 | Surface tension of aqueous solutions of water-soluble organic and inorganic compounds 显示文摘 | Tuckermann R | 2007 | Atmospheric Environment2007,41,29: | 1 |
| 4 | Glucocorticoid receptor ac- tion in beneficial and side effects of steroid therapy: les- sons from conditional knockout mice显示文摘 | Kleiman A Tuckermann J P | 2007 | Mol Cell Endocrinol2007,275,1: | 1 |
| 5 | DOAS-observation of halogen radical-catalysed Arctic boundary layer ozone destruction during the ARCTOC campaigns 1995 and 1996 in Ny-Alesund, Spitsbergen显示文摘 | Tuckermann M Ackermann R Golz C | 1997 | Tellus1997,49,: | 1 |
| 6 | Glucocorticoid receptor action in beneficial and side effects of steroid therapy: lessons from conditional knockout mice 显示文摘 | Kleiman A Tuckermann J P | 2007 | Mol Cell Endocrinol2007,275,12: | 1 |
| 7 | Calgranulins S100A8 and S100A9 are negatively regulated by glucocorticoids in ac-Fos-dependent manner and overexp ressed throughout skin carcinogenesis 显示文摘 | Gebhardt C Breitenbach U Tuckermann JP | 2002 | Oncogene2002,21,: | 1 |
| 8 | Macrophages and neutrophils are the targets forimmune suppression by glucocorticoids in contact allergy显示文摘 | Tuckermann J P Kleiman A Moriggl R Spanbroek R Neumann A Illing A | 2007 | J Clin Invest2007,117,5: | 1 |
| 9 | Jun B required for IgE-mediated degranulation and cytokine release of mast cells显示文摘 | Textor B Licht AH Tuckermann JP | 2007 | J Immunol2007,179,10: | 1 |
| 10 | The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism显示文摘 | Labrador J P Azcoitia V Tuckermann J | 2001 | EMBO Rep2001,2,5: | 1 |
| 11 | Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones显示文摘 | Maes C Goossens S Bartunkova S Drogat B Coenegrachts L Stockmans I Moermans K Nyabi O Haigh K Naessens M Haenebalcke L Tuckermann JP Tjwa M Carmeliet P Mandic V David J-P Behrens A Nagy A Carmeliet G Haigh JJ | | 0,,: | 1 |
| 12 | Could a phase model help to improve translational animal research?显示文摘Background:Animal models are widely applied in medical research for different purposes.In particular,results from translational experiments may be used for subsequent clinical development.However,transferability of these findings to the human organism is controversial.Among other factors,this may be traced back to a lack of clear differentiation of the evidence(explorative vs.confirmatory)provided by such experimental results.In general,inferential statistics(i.e.p values)should not be interpreted in as confirmatory unless crucial methodological requirements are met.Methods:Therefore,we propose a phase model which reflects the well-established process of clinical research,and we discuss its potential to improve decision making in translational research.The model aims to clarify the reliability of results derived from animal models.Results:The phase model proposes subdividing translational,pre-clinical research into pilot,exploration,and confirmation phases.Experiments for which there is no valid estimation of the expected effect size are designated as pilot studies.Based on these data,experiments in subsequent phases may be planned using both appropriate design and statistical methods.Conclusion:Separating the entire process of translational animal research into three phases could contribute to improved transparency of the evidence derived from such experiments. | Benjamin Mayer Jan Tuckermann Rainer Muche | 2022 | Animal Models and Experimental Medicine2022,5,6: | 1 |
| 13 | Optimized Convective Cooling Using Micromachined Structure显示文摘 | Tuckermann D B Pease R F | 1982 | Electro-chemical Society1982,129,3: | 1 |
| 14 | The role of the glucocorticoid receptor in inflammation and immunity 显示文摘 | Baschant U Tuckermann J | 2010 | J Steroid Biochem Mol Biol2010,120,23: | 1 |
| 15 | DNA binding of the glucocorticoid receptor is not essential for survival 显示文摘 | Reichardt HM Kaestner KH Tuckermann J | 1998 | Cell1998,93,4: | 1 |
| 16 | Calgranulins S100A8 and S100A9 are negatively regulated by gtucocorticoids in a c-Fos- dependent manner and overexpressed throughout skin carcinogenesis显示文摘 | Gebhardt C Breitenbach U Tuckermann JP | 2002 | Oncogene2002,21,27: | 1 |
| 17 | Molecular mechanisms of glucocorticoids in the control of inflammation and lymphocyte apoptosis显示文摘 | Tuckermann JP Kleiman A McPherson KG | 2005 | Crit Rev Clin Lab Sci2005,42,1: | 1 |
| 18 | The role of the glucocorti- coid receptor in inflammation and immunity 显示文摘 | Baschant U Tuckermann J | 2010 | J Ster- oid Biochem Mol Biol2010,120,23: | 1 |
| 19 | New insights into the anti - inflammatory mechanisms of glucocorticoids: an emer- ging role for glucocorticoid - receptor - mediated transactivation 显示文摘 | Vandevyver S Dejager L Tuckermann J | 2013 | Endocrinology2013,154,3: | 1 |
| 20 | DNA binding of the glucocorticoid receptor is not essential for survival 显示文摘 | Reichardt H M Kaestner K H Tuckermann J | 1998 | Ce111998,93,4: | 1 |