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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 | 卒中介入治疗培训指南:国际多学会共识文件显示文摘1背景
缺血性卒中是全球人口死亡和残疾的首要原因。很多急性大血管闭塞(emergent large vesselocclusion,ELVO)患者都会遗留长期残疾。事实上,这些颅内大动脉闭塞经常会导致大面积脑损伤,进而造成患者死亡或严重致残。 | Lavine SD Cockroft K Hoh B Bambakidis N Khalessi AA Woo H Riina H Siddiqui A Hirsch JA Chong W Rice H Wenderoth J Mitchell P Coulthard A Signh TJ Phatorous C Khangure M Klurfan P ter Brugge K Iancu D Gunnarsson T Pongpech S Rodesch G Soderman M Taylor A Krings T Orbach D Picard L Suh DC Zheng HQ Jansen O Muto M Szikora I Pierot L Brouwer P Gralla J Renowden S Andersson T Fiehler J Turjman F White P Januel AC Spelle L Kulcsar Z Chapot R Biondi A Dima S Taschner C Szajner M Krajina A Sakai N Matsumaru Y Yoshknura S Ezura M Fujinaka T Iihara K Ishii A Higashi T Hirohata M Hyodo A Ito Y Kawanishi M Kiyosue H Kobayashi E Kobayashi S Kuwayama N Matsumoto Y Miyachi S Murayama Y Nagata I Nakahara I Nemoto S Niimi Y Oishi H Satomi J Satow T Sugiu K Tanaka M Terada T Yamagami H Diaz O Lylyk P Jayaraman MV Patsalides A Gandhi CD Lee SK Abruzzo T Albani B Ansari SA Arthur AS Baxter BW Bulsara KR Chen M Almandoz JE Fraser JF Heck DV Hetts SW Hussain MS Klucznik RP Leslie-Mawzi TM Mack WJ McTaggart RA Meyers PM Mocco J Prestigiacomo CA Pride GL Rasmussen PA Starke RM Sunenshine PJ Tarr RW Frei DF Pabo M Nogueira RG Zaidat OO Jovin T Linfante I Yavagal D Liebeskind D Novakovic R Pongpech S 许岩 孙瑞 郭芮兵 | 2017 | 国际脑血管病杂志2017，25，5： | 2 |
| 3 | Gastrointestinal: Asymptomatic rectal perforation and massive pneumoretroperitoneum in patient with ulcerative colitis treated with mesalamine enemas显示文摘 | YS Choi IT Lee KR Cho JK Kim JP Suh DS Lee | 2013 | J Gastroenterol Hepatol2013，，7： | 2 |
| 4 | Dose optimization of intravenous magnesium sulfate after acute stroke显示文摘 | Lees KR | 1998 | Stroke1998，29，： | 1 |
| 5 | NXY-059 for acute ischemic stroke显示文摘 | Zivin JA Ashwood T | 2006 | N Engl J Med2006，354，： | 1 |
| 6 | Differences in first dose responseto angiotension coventing enzyme inhibition in congestive heart failure:a placebo controlled study显示文摘 | Lees KR Reid JL | 1991 | Br Heart J1991，66，： | 1 |
| 7 | The role of the coagulation cascadein brain edema formation after intracerebral hemorrhage显示文摘 | Lee KR Betz AL Kim S | 1996 | Acta Neurochir1996，138，4： | 1 |
| 8 | Pre-operative chemoradiation pancreaticoduodenectomy and intraoperative radiation therapy for adenocarcinoma of the pancreatic head 显示文摘 | Staley CA Lee JE Cleary KR | 1996 | Ann J Surg1996，171，： | 1 |
| 9 | Output feedback robust H∞ control of uncertain fuzzy dynamic systems with time-varying delay 显示文摘 | LEE KR KIM JH JEUNG ET | 2000 | IEEE Trans on Fuzzy Systems2000，8，6： | 1 |
| 10 | Machanisms of edema formation after intracerebral hemorrhage: Effects of thrombin on cerebral blood flow, blood - brain barrier permeability and cell survival in a rat model 显示文摘 | Lee KR Kawal N Kim S | 1997 | J Neurosurgery1997，46，： | 1 |
| 11 | Duration of neuroprotective treatmemt for ischemic stroke显示文摘 | Dyker AG Lees KR | 1998 | Stroke1998，29，： | 1 |
| 12 | Interatrial septal abnormalities and stroke:a meta-analysis of case-control studies显示文摘 | Overell JR Bone I Lees KR | 2000 | Neurology2000，55，8： | 1 |
| 13 | Pulmonary small lymphocytic lymphoma ( mucosa-associated lymphoid tissue type) associated with pulmonary hyalinizing granuloma 显示文摘 | Ren YF Raitz EAN Lee KR | 2001 | Chest2001，120，3： | 1 |
| 14 | Mechanisms of edema formation after intracerebral hemorrhage:effects of thrombin on cerebral blood flow,blood-brain barrier permeability,and cell servival in a rat model显示文摘 | Kawai N Kim S | 1997 | J Neurosurg1997，86，： | 1 |
| 15 | Advances in emerging therapies 2006显示文摘 | Dawson J | 2007 | Stroke2007，38，： | 1 |
| 16 | Duration of neuroprotective treatmemt for ischemic stroke显示文摘 | Dyker AG Lees KR | 1998 | Stroke1998，29，： | 1 |
| 17 | The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage显示文摘 | Lee KR Betz AL Kim S | 1996 | Acta Neurochir1996，138，： | 1 |
| 18 | Edema from intracerebral hemorrhage:the role of thrombin显示文摘 | Lee KR Colon GP Betz AL | 1996 | J Neurosurg1996，84，： | 1 |
| 19 | Interatrial septal abnormalities and stroke:A meta-analysis of case-control studies显示文摘 | Overell JR Bone I Lees KR | 2000 | Neurology2000，55，： | 1 |
| 20 | Pulmonary benign metastasizing leiomyoma associated with intravenous leiomyomatosis of the uterus : clinical be- havior and genomic changes supporting a transportation theory 显示文摘 | Lee HJ Choi J Kim KR | 2008 | Int J Gynecol Pathol2008，27，3： | 1 |
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