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您的检索式：作者名="Jingting Lin"
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| 1 | Sustained Akt signaling in articular chondrocytes causes osteoarthritis via oxidative stress-induced senescence in mice显示文摘Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus.Genetic mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^(ERT2) developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient mice.Mechanistically, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore,inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA. | Jing Xie Jingting Lin Min Wei Yan Teng Qi He Guan Yang Xiao Yang | 2019 | Bone Research2019，7，3： | 8 |
| 2 | Odontoblast β-catenin signaling regulates fenestration of mouse Hertwig's epithelial root sheath显示文摘The interaction between Hertwig's epithelial root sheath(HERS) and the adjacent mesenchyme is vitally important in mouse tooth root development. We previously generated odontoblast-specific Ctnnb1(encoding β-catenin) deletion mice, and demonstrated that odontoblast β-catenin signaling regulates odontoblast proliferation and differentiation. However, the role of odontoblast β-catenin signaling in regulation of HERS behavior has not been fully investigated. Here, using the same odontoblast-specific Ctnnb1 deletion mice, we found that ablation of β-catenin signaling in odontoblasts led to aberrant HERS formation. Mechanistically, odontoblast-specific Ctnnb1 deletion resulted in elevated bone morphogenetic protein 7(Bmp7) expression and reduced expression of noggin and follistatin, both of which encode extracellular inhibitors of BMPs. Furthermore, the levels of phosphorylated Smad1/5/8 were increased in HERS cells. In vitro tissue culture confirmed that BMP7 treatment disrupted the HERS structure. Taken together, we demonstrated that odontoblast β-catenin signaling may act through regulation of BMP signaling to maintain the integrity of HERS cells. | ZHANG Ran TENG Yan ZHU Liang LIN JingTing YANG Xiao YANG Guan LI TieJun | 2015 | Science China(Life Sciences)2015，58，9： | 8 |
| 3 | Biliary excretion and enterohepatic circulation of thienorphine and its glucuronide conjugate in rats显示文摘Thienorphine(TNP)is a new partial opioid agonist currently developed as a promising drug candidate with the intended clinical indication for the treatment of opioid dependence.The pharmacokinetic profile and biliary excretion of TNP and its glucuronide conjugate(TNP-Glu)were investigated after oral administration of TNP in rats.The concentrations of TNP and TNP-Glu were simultaneously quantified using a LC-MS/MS method.A double peak phenomenon was observed in TNP plasma concentration–time curves with the secondary peak appeared at 6–8 h.A slower decline of plasma concentrations in the terminal phase was observed for TNP with T1/2 of 7.01 h.TNP-Glu was the predominant component in rat plasma and bile.Its plasma level was about 10 times higher than TNP and the 24 h accumulative bile excretion rate was 23%.Enterohepatic circulation of TNP and TNP-Glu was evaluated using a paired rat model.In bile-donor rats,no double-peak was detected and the elimination half life of TNP was significantly shortened(3.71 h)when compared to intact rats(7.01 h,P<0.05).Both TNP and TNP-Glu were detected in bile-recipient rats.Their exposures in recipient rats due to enterohepatic circulation were 15.6%and 42.6%for the parent drug and the metabolite,respectively.The deconjugation of the glucuronide conjugate and the reabsorption of free TNP were further confirmed in in situ perfused rat intestinal preparations.These results indicate that the enterohepatic circulation has a significant influence on the systemic exposure of the parent drug and its glucuronide conjugate,particularly on the terminal elimination of TNP,which may result in the prolonged retention of the drug in body. | Jingting Deng Xiaomei Zhuang Guolin Shen Hua Lin Zehui Gong | 2012 | Acta Pharmaceutica Sinica B2012，2，2： | 0 |
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