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| 1 | SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity显示文摘Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor(OCP), and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2(encoded by Ptpn11) affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using 'Cre-lox P'-mediated gene excision.SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts. Consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1, and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, q RT-PCR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration. | Chunlin Zuo Lijun Wang Raghavendra M.Kamalesh Margot E.Bowen Douglas C.Moore Mark S.Dooner Anthony M.Reginato Qian Wu Christoph Schorl Yueming Song Matthew L.Warman Benjamin G.Neel Michael G.Ehrlich Wentian Yang | 2018 | Bone Research2018，6，2： | 3 |
| 2 | Influence of the crude oil resin/asphaltene ratio on the stability of oil/water emulsions 显示文摘 | Schorling P C Kessel D G Rahimian I | 1999 | Colloids Surfaces A: Physicochemical and Engineering Aspects1999，152，： | 1 |
| 3 | C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Laglp and Lac1p显示文摘 | Guillas T Schorling S | 2001 | EMBO J2001，20，11： | 1 |
| 4 | Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae显示文摘 | SCHORLING S VALLEE B BARZ WP | 2001 | Mol Biol Cell2001，12，11： | 1 |
| 5 | A mindfulness course decreases burnout and improves well-being among healthcare providers显示文摘 | Goodman M J Schorling J B | 2012 | Int J Psychiatry Med2012，43，2： | 1 |
| 6 | Transcription factor AP-2 essential for cranial closure andcraniofacial development显示文摘 | SCHORLE H MEIER P BUCHERT M | 1996 | Nature1996，381，： | 1 |
| 7 | A subtractive gene expression screen suggests a role of transcription factor AP- 2 alpha in eontrol of proliferation and differentiation显示文摘 | Pfisterer P Ehlermann J Hegen M Schorle H | 2002 | J Biol Chem2002，277，8： | 1 |
| 8 | Influence of the crude oil/water emulsions显示文摘 | SCHORLING P C KESSEL D G | 1999 | Colloids and Surfaces1999，152，： | 1 |
| 9 | Tobacco, alcohol and other drug use among college students 显示文摘 | Schorling JB Gutgesell M Klas P | 1994 | J Subst Abuse1994，6，1： | 1 |
| 10 | Transcription factor AP-2 essential for cranial closure and craniofacial de- velopment 显示文摘 | SCHORLE H MEIER P BUCHERT M | 1996 | Nature1996，381，： | 1 |
| 11 | Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene显示文摘 | Sadlack B Merz H Schorle H | 1993 | Cell1993，75，2： | 1 |
| 12 | Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting显示文摘 | Schorle H Holtschke T Hunig T | 1991 | Nature1991，352，： | 1 |
| 13 | Ulcerative colitis- like disease in mice with a disrupted interleukin-2 gene显示文摘 | Sadtack B Merz H Schorle H | 1993 | Ceil1993，75，： | 1 |
| 14 | A mindfulness course decrea- ses burnout and improves well-being among healthcare providers显示文摘 | Goodman MJ Schorling JB | 2012 | Int J Psychiatry Med2012，43，2： | 1 |
| 15 | Malnutrition is associated with increased diarrhea incidence and duration among children in an urban bratilian slum显示文摘 | Schorling JB Mc Acliffe JF De Soaza MA | 1990 | Int Epidemiol1990，19，： | 1 |
| 16 | Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene 显示文摘 | Sadlack B Merz H Schorle H | 1993 | Cell1993，75，2： | 1 |
| 17 | Effect of asphaltene and resins on the stability of water-in-waxy oil emulsions 显示文摘 | Zaki N Schorling P C Rahimian I | 2000 | PetSci Technol2000，18，： | 1 |
| 18 | Potential role of adherence traits of Escherichia coli in persistent diarrhea in an urban Brazilian slum显示文摘 | Schorling J B Barrett L J | 1991 | Pediatr Infect Dis J1991，10，： | 1 |
| 19 | Treatment of upper respiratory infections:Do patients really want antibiotics?显示文摘 | Philbrick JT` Schorling JB | 1999 | Amer J Med1999，107，5： | 1 |
| 20 | HE4 promotes collateral resistance to cisplatin and paclitaxel in ovarian cancer cells显示文摘 | Ribeiro JR Schorl C Yano N | 2016 | J Ovarian Res2016，9，1： | 1 |
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