scholarly journals TGF-β prevents the denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhen Yu ◽  
Ye Li ◽  
Yining Wang ◽  
Yuting Chen ◽  
Mengfan Wu ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Transforming Growth Factor Beta ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Multifunctional Protein ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Tgf Β1

Abstract Background: Transforming growth factor beta (TGF-β) can stimulate osteogenesis as a multifunctional protein. The present study was to explore if TGF-β can prevent denervation-induced reduction of bone formation. Materials & methods: The 6-week-old male mice were treated with recombinant human TGF-β1 (rhTGF-β1). Bone formation, endochondral bone growth rates, and gene expression of osteoblast markers were measured in the skeletal tissue by real-time PCR. Results: RhTGF-β1 treatment prevented the denervation-induced decrease in bone formation rates, endochondral growth, and expression of Cbfa1/Runx2 (runt-related transcription factor 2), Ostecalcin (OC), and ColIA1. TGF-β1 partially inhibited the denervation-induced ubiquitination of Cbfa1/Runx2 in mouse cancellous bones via ubiquitin-proteasome pathway. Conclusion: TGF-β prevents denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway at least partially.

scholarly journals Ubiquitination and Proteolysis of Cancer-Derived Smad4 Mutants by SCFSkp2

2004 ◽  
Vol 24 (17) ◽  
pp. 7524-7537 ◽  
Author(s):  
Min Liang ◽  
Yao-Yun Liang ◽  
Katharine Wrighton ◽  
Dana Ungermannova ◽  
Xiao-Ping Wang ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Human Cancer ◽  
Antibody Array ◽  
Interacting Proteins ◽  
Ubiquitin E3 Ligase ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Growth Factor Beta ◽  
Common Signal

ABSTRACT Smad4/DPC4, a common signal transducer in transforming growth factor beta (TGF-β) signaling, is frequently inactivated in human cancer. Although the ubiquitin-proteasome pathway has been established as one mechanism of inactivating Smad4 in cancer, the specific ubiquitin E3 ligase for ubiquitination-mediated proteolysis of Smad4 cancer mutants remains unclear. In this report, we identified the SCFSkp2 complex as candidate Smad4-interacting proteins in an antibody array-based screen and further elucidated the functions of SCFSkp2 in mediating the metabolic instability of cancer-derived Smad4 mutants. We found that Skp2, the F-box component of SCFSkp2, physically interacted with Smad4 at the physiological levels. Several cancer-derived unstable mutants exhibited significantly increased binding to Skp2, which led to their increased ubiquitination and accelerated proteolysis. These results suggest an important role for the SCFSkp2 complex in switching cancer mutants of Smad4 to undergo polyubiquitination-dependent degradation.

scholarly journals Ligand-dependent Degradation of Smad3 by a Ubiquitin Ligase Complex of ROC1 and Associated Proteins

2001 ◽  
Vol 12 (5) ◽  
pp. 1431-1443 ◽  
Author(s):  
Minoru Fukuchi ◽  
Takeshi Imamura ◽  
Tomoki Chiba ◽  
Takanori Ebisawa ◽  
Masahiro Kawabata ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Ring Finger ◽  
Transforming Growth Factor Β ◽  
Dependent Manner ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Ligase Complex ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Smads are signal mediators for the members of the transforming growth factor-β (TGF-β) superfamily. Upon phosphorylation by the TGF-β receptors, Smad3 translocates into the nucleus, recruits transcriptional coactivators and corepressors, and regulates transcription of target genes. Here, we show that Smad3 activated by TGF-β is degraded by the ubiquitin–proteasome pathway. Smad3 interacts with a RING finger protein, ROC1, through its C-terminal MH2 domain in a ligand-dependent manner. An E3 ubiquitin ligase complex ROC1-SCFFbw1a consisting of ROC1, Skp1, Cullin1, and Fbw1a (also termed βTrCP1) induces ubiquitination of Smad3. Recruitment of a transcriptional coactivator, p300, to nuclear Smad3 facilitates the interaction with the E3 ligase complex and triggers the degradation process of Smad3. Smad3 bound to ROC1-SCFFbw1a is then exported from the nucleus to the cytoplasm for proteasomal degradation. TGF-β/Smad3 signaling is thus irreversibly terminated by the ubiquitin–proteasome pathway.

scholarly journals A potential therapy of human umbilical cord mesenchymal stem cells for bone regeneration on osteoporotic mandibular bone

2018 ◽  
Vol 12 (03) ◽  
pp. 358-362
Author(s):  
Nike Hendrijantini ◽  
Tuti Kusumaningsih ◽  
Rostiny Rostiny ◽  
Pungky Mulawardhana ◽  
Coen Pramono Danudiningrat ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Umbilical Cord ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Control Group Design ◽  
Mandibular Bone ◽  
Female Wistar Rats ◽  
Tgf Β1

ABSTRACTObjective: The aim of this study is to prove that human umbilical cord mesenchymal stem cell (hUCMSC) therapy on mandibular osteoporotic model is able to increase transforming growth factor-beta-1 (TGF)-β1 expression, Runx2, and osteoblasts. Materials and Methods: This research is true experimental posttest control group design. Thirty female Wistar rats were divided into 6 groups randomly, which consisted of sham surgery for control (T1), ovariectomy as osteoporotic group (T2), osteoporotic group injected with gelatine for 4 weeks (T3), 8 weeks (T4) injected with hUCMSC-gelatine for 4 weeks (T5) and 8 weeks (T6). All mice were presented for immunohistochemistry examination for TGF-β1, Runx2, and histology for osteoblasts. Results: The lowest level of osteoblast was osteoporotic group injected with gelatine in 4 weeks compared to other groups. There were increases of TGF-β1, Runx2, and osteoblasts from osteoporotic group compared to osteoporotic post-hUCMSC-gelatine injection group. Conclusion: The hUCMSC has a high osteogenic effect and increases the osteoporotic mandibular bone regeneration on the animal model that is showed by the increase of the level of TGF-β1, Runx2, and osteoblasts.

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