【摘 要】
：
Multiple constitutively active mutations of FGFR3 can lead to achondroplasia (ACH), one of the most common dwarfisms in humans, but the molecular mechanism remains elusive.In this study, we found that
【机 构】
：
State Key Laboratory of Trauma, Burns and Combined Injury, Center of Bone Metabolism and Repair, Tra
【出 处】
：
3rd International Conference on Fibroblast Growth Factors (F
论文部分内容阅读
Multiple constitutively active mutations of FGFR3 can lead to achondroplasia (ACH), one of the most common dwarfisms in humans, but the molecular mechanism remains elusive.In this study, we found that FGFR3 inhibiting AKT1 signaling contributes to the progress of bone development related to ACH.FGFR3 directly binds unphosphorylated AKT1, but not the constitutive activated form, to facilitate its degradation through CHIP-mediated ubiquitination pathway.Using in vitro embryonic bone culture system, we showed that BpV, a specific inhibitor of PTEN, increased the growth of cultured bone rudiment.Furthermore, we demonstrated that PTEN ablation in chondrocytes rescued the bone phenotype observed in FGFR3 knock-in mice by increasing chondrocyte proliferation and differentiation.Our findings reveal that FGF/FGFR3 plays an important role in the regulation of chondrogenesis and development of achondroplasia by booting the degradation of unphosphorylated AKT1.
其他文献
Exact cause of fibroids is not known & especially the impact on infertility is less evaluated.Ongoing research on fibroids shows high level of aromatase hence hyperestrogenemia.We also noticed that fi
Purpose: Although laparoscopy remains to be the gold standard for the evaluation of fallopian tubes, the process cannot be used to directly observe the inner cavity of the fallopian tube.Salpingoscopy
Background:Activated Protein C (APC) is a natural anticoagulant protein, with recently discovered anti-inflammatory and anti-apoptotic effects.We recently unveiled that APC can limit cardiac ischemia/
There is a growing body of evidence showing that FGFRs can be targeted to the nucleus.We investigate FGFR signalling in breast and pancreatic cancer cell line models, complementing these studies with
The functions of a large number (> 435) of extracellular regulatory proteins are controlled by their interactions with heparan sulfate (HS).In the case of fibroblast growth factors (FGFs), HS binding
In spite of the well-established angiogenic function in vitro, and in vivo evidence suggesting that FGF signaling is important for both normal physiological and pathological responses of the vascular
Clinical translation of growth factor therapies faces multiples challenges;the most significant is how to maintain bioactivity.My lab uses heparin and a biocompatible polycation to form an injectable
Stromal cell derived factor 1 (SDF-1/CXCL 12) and C-X-C chemokine receptor type 4 (CXCR4) axis plays a critical role in vascular injury recovery and angiogenesis.However, the multi-functional characte
Dysregulation of heparan-sulfate proteoglycan (HSPG) biosynthetic enzymes plays a critical role at various stages of tumorigenesis and we have recently shown that, in the chondrosarcoma cell line H-HE