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| 1 | A novel negative regulatory mechanism of Smurf2 in BMP/Smad signaling in bone显示文摘Transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)play important roles in bone metabolism.Smad ubiquitination regulatory factors(Smurfs)regulate TGF-β/BMP signaling via ubiquitination,resulting in degradation of signaling molecules to prevent excessive activation of TGF-β/BMP signaling.Though Smurf2 has been shown to negatively regulate TGF-β/Smad signaling,its involvement in BMP/Smad signaling in bone metabolism has not been thoroughly investigated.In the present study,we sought to evaluate the role of Smurf2 in BMP/Smad signaling in bone metabolism.Absorbable collagen sponges containing 3μg of recombinant human BMP2(rhBMP2)were implanted in the dorsal muscle pouches of wild type(WT)and Smurf2−/−mice.The rhBMP2-induced ectopic bone in Smurf2−/−mice showed greater bone mass,higher mineral apposition and bone formation rates,and greater osteoblast numbers than the ectopic bone in WT mice.In WT mice,the ectopic bone consisted of a thin discontinuous outer cortical shell and scant inner trabecular bone.In contrast,in Smurf2−/−mice,the induced bone consisted of a thick,continuous outer cortical shell and abundant inner trabecular bone.Additionally,rhBMP2-stimulated bone marrow stromal cells(BMSCs)from Smurf2−/−mice showed increased osteogenic differentiation.Smurf2 induced the ubiquitination of Smad1/5.BMP/Smad signaling was enhanced in Smurf2−/−BMSCs stimulated with rhBMP2,and the inhibition of BMP/Smad signaling suppressed osteogenic differentiation of these BMSCs.These findings demonstrate that Smurf2 negatively regulates BMP/Smad signaling,thereby identifying a new regulatory mechanism in bone metabolism. | Junichi Kushioka Takashi Kaito Rintaro Okada Hiroyuki Ishiguro Zeynep Bal Joe Kodama Ryota Chijimatsu Melanie Pye Masahiro Narimatsu Jeffrey LWrana Yasumichi Inoue Hiroko Ninomiya Shin Yamamoto Takashi Saitou Hideki Yoshikawa Takeshi Imamura | 2020 | Bone Research2020，8，4： | 6 |
| 2 | Dust transport and questions of desert loess formation 显示文摘 | Tsoar H Pye K | 1987 | Sedimentology1987，34，： | 1 |
| 3 | Effect of passive smoking on pulmonary function in the asthmatic child显示文摘 | CALLEN BM GONZALEZ PYE | 1997 | An Esp Pediatr1997，47，： | 1 |
| 4 | Laboratory evaluation of temperature effects on the germination and growth of entomopathogenic fungi and on their pathogenicity to two aphid species显示文摘 | Yeo H Pell J K Alderson P G Clark S J Pye B J | 2003 | Pest Manage Sci2003，59，： | 1 |
| 5 | A Vibration Technique for Non-Destructively Assessing the Integrity of Structures显示文摘 | Adams R D Cawley P Pye C J | 1978 | Journal of Mechanical Engineering Science1978，，20： | 1 |
| 6 | A comparable study of organosolv and kraft pulps显示文摘 | Lora J H Pye E K | 1994 | Pulp and Paper1994，，2： | 1 |
| 7 | Radiographic features of lumbar disc degeneration and bone mineral density in men and women 显示文摘 | Pye SR Reid DM Adams JE | 2006 | Ann Rheum Dis2006，65，2： | 1 |
| 8 | Regulation of FGF - 1 mitogenic activity by heparan sulfate oligosaceharides is dependent on specific structural features: differential requirements for the modulation of FGF -1 and FGF-2显示文摘 | Pye DA Vives RR Hyde P | 2000 | Glycobiology2000，10，11： | 1 |
| 9 | A vibration technique for non - destructive assessing the integrity of structures显示文摘 | Cawley P Pye C J Stone B J | 1978 | Journal of Mechanical Engineering Science1978，20，： | 1 |
| 10 | Bauxites gathering dust 显示文摘 | Pye K | 1988 | Nature1988，333，： | 1 |
| 11 | QT inteval dispersion:a non-invasivemarker of susceptibility to arrhythmia in patients with sustained ventrhythmia显示文摘 | Pye M Quinn AC Cobbe SM | 1994 | Br Heart J1994，71，7： | 1 |
| 12 | Regulation of FGF-1 mitogenic activity by heparan sulfateoligosaccharides is dependent on specific structural features:differential requirementsfor the modulation of FGF-1 and FGF-2显示文摘 | Pye DA Vives RR Hyde P | 2000 | Glycobiology2000，10，11： | 1 |
| 13 | Adaptiveness of echolocation in bats:Flexibility in behavior andin evolution显示文摘 | PYE J D | 1980 | Trends in Neurosciences1980，3，： | 1 |
| 14 | GRADISTAT:A grain size distribution and statistics package for the analysis of unconsolidated sediments显示文摘 | BLOTT S J PYE K | 2001 | Earth Surface Processes and Landforms2001，26，11： | 1 |
| 15 | A vibration technique for non-destructively assessing the integrity of structures显示文摘 | ADAMS R D CAWLEY P PYE C J | | 0，，2： | 1 |
| 16 | Sediment logy of coarseclastic beach-ridge deposits, Essex, southeast England 显示文摘 | ADRIAN NEAL JULIE RICHARDS KEN PYE | 2003 | Sedimentary Geology2003，162，： | 1 |
| 17 | Breast carcinoma:comparative study of tumor vasculature using two endothelial cell markers显示文摘 | Wang J M Kumar S Pye D | 1994 | J Natl Cancer Inst1994，86，5： | 1 |
| 18 | Color-coded ultrasound diagnosis of vascular occlusion in acute ischemic stroke显示文摘 | Martin P Pye I Abbott R | 1995 | J Neuroimaging1995，5，： | 1 |
| 19 | GRADISTAT:grain size distribution and statistics package for the analysis of unconsolidated sediments显示文摘 | BIott S J Pye K | 2001 | Earth Surfaces Processes and Landforms2001，26，： | 1 |
| 20 | Under-standing broad scale wildfire risks in a human-dominated land-scape显示文摘 | PRESTEMON J P PYE J M BUTRY D T | 2002 | Forest Science2002，48，： | 1 |
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