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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 | Terminology-driven mining of biomedical literature 显示文摘 | Nenadic G Spasic I Ananiadou S | 2003 | Bioinformatics2003，19，8： | 1 |
| 3 | SWOT Analysis of Serbia and Montenegro's Accession to the EU 显示文摘 | Jurij Bajec Nikola Fabris Jelena Galic Svedana Mitrovic Marina Spasic | 2004 | Transition Studies Review2004，11，3： | 1 |
| 4 | AMP-activated protein kinase (AMPK) molecular crossroad for metabolic control and survival of neurons显示文摘 | Spasic Callaerts P Norga KK | 2009 | Neuroscientist2009，15，4： | 1 |
| 5 | Surrogate data test for nonlinearity of the rat cerebellar electrocorticogram in the model of brain injury显示文摘 | Spasic Sladana | 2010 | Signal Processing2010，90，12： | 1 |
| 6 | Oxidative stress in diabetic pregnancy: SOD, CAT and GSH-Px activity and lipid peroxidation products显示文摘 | A Djordjevic S Spasic A Jovanovic-Galovic R Djordjevic G Grubor-Lajsic | 2004 | Journal of Maternal-Fetal and Neonatal Medicine2004，，6： | 1 |
| 7 | Surrogate data modeling the relationship between high frequency amplitudes and higuchi fractal dimension of eeg signals in anesthetized rats显示文摘 | Spasic S Kalauzi A Kesic S Obradovic M Saponjic J | | 0，，： | 1 |
| 8 | P ( PON1 ) activity, but not PON1 (Q192R) phenotype, is a predictor of coronary, artery disease in a middle-aged Serbian population 显示文摘 | Kotur-Stevuljevic J Spasic S Stefanovic A | 2006 | Clin Chem Lab Med2006，44，10： | 1 |
| 9 | Clinical performances of the EuroSCOREⅡin a single-centre, contemporary cardiac surgical cohort 显示文摘 | Nezic D Spasic T Micovic S | 2015 | J Cardiothorac Surg2015，10，1： | 1 |
| 10 | The effects of remaining axons on motorneuron survival and NOS expression following axotomy in adult rats显示文摘 | Gu Y SPASIC Z WU W | 1997 | Dev Neurosic1997，19，3： | 1 |
| 11 | The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice 显示文摘 | Casanovas G Vuji6 Spasic M Casu C | 2013 | Haematologica2013，98，3： | 1 |
| 12 | STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation显示文摘 | Verga Falzacappa MV Vujic Spasic M Kessler R | 2007 | Blood2007，109，1： | 1 |
| 13 | Relation- ship between bone resorption, oxidative stress and inflamma- tion in severe COPD exacerbation 显示文摘 | Stanojkovic I Kotur-Stevuljevic J Spasic S | 2013 | Clin Biochem2013，20，00： | 1 |
| 14 | Epileptic seizures due to multiple cerebral cavernomatosis显示文摘 | Spasic M Lukic S | 2007 | Vojnosanit Pregl2007，64，7： | 1 |
| 15 | Pineal cyst: a review of clinical and radiologieal features显示文摘 | Choy W Kim W Spasic M | 2011 | Neurosurg Clin N Am2011，22，3： | 1 |
| 16 | The effects of remaining axons on motoneuron survival and NOS expression following axotomy in the adult rat 显示文摘 | Gu Y Spasic Z Wu W | 1997 | J Dev Neurosci1997，19，3： | 1 |
| 17 | Optimization of a free separation of 30 free amino acids and peptides by capillary zone electrophoresis with indirect absorbance detection:a potential for quantification in physiological fluids显示文摘 | Zunic G Zorana J I Colic M Spasic S | 2002 | Chromatogr B2002，，772： | 1 |
| 18 | Expanding rolesfor AMP-activated protein kinase in neuronal survival and autoph-agy显示文摘 | POELS J SPASIC MR CALLAERTS P | 2009 | Bioessays2009，31，9： | 1 |
| 19 | Termnology-driven mining of biomedical literature显示文摘 | SPASIC f ANANIADOU S | 2003 | Journal of Biomedical Informatics2003，，33： | 1 |
| 20 | Trophoblastic oxidative stress and the release of cell-free feto-placental DNA显示文摘 | Tjoa M L Cindrova D T Spasic B O | 2006 | Am J Pathol2006，169，2： | 1 |
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