E3 Ubiquitin Ligase-Mediated Regulation of Osteoblast Differentiation and Bone Formation

Shen, Jianlin; Fu, Bowen; Li, Yanfang; Wu, Yanjiao; Sang, Hongxun; Zhang, Heshi; Lin, Hua; Liu, Huan; Huang, Wenhua

doi:10.3389/fcell.2021.706395

Cited by 20 publications

(20 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most relevant pathways of upregulated proteins again included cell cycle checkpoints, mitotic transitions, and signal transduction (again Wnt signaling and negative regulation of Notch4 signaling, with the absence of HH signaling) (Figure S8C). These upregulated terms and pathways suggest that topography promoted cell proliferation and mitosis, hASC osteodifferentiaton by impacting Wnt, Notch, and HH signaling, − and additional ubiquitin ligase-mediated regulation, key for osteoblast differentiation . The DReg-TopoOST proteins were enriched in GO terms related to protease binding, cell-substrate adhesion, cell–matrix adhesion, and actin-binding (Figure B).…”

Section: Resultsmentioning

confidence: 97%

Bioengineered Hierarchical Bonelike Compartmentalized Microconstructs Using Nanogrooved Microdiscs

Bjørge

Sousa

Patrício

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Fabrication of vascularized large-scale constructs for regenerative medicine remains elusive since most strategies rely solely on cell self-organization or overly control cell positioning, failing to address nutrient diffusion limitations. We propose a modular and hierarchical tissue-engineering strategy to produce bonelike tissues carrying signals to promote prevascularization. In these 3D systems, disc-shaped microcarriers featuring nanogrooved topographical cues guide cell behavior by harnessing mechanotransduction mechanisms. A sequential seeding strategy of adipose-derived stromal cells and endothelial cells is implemented within compartmentalized, liquefied-core macrocapsules in a self-organizing and dynamic system. Importantly, our system autonomously promotes osteogenesis and construct’s mineralization while promoting a favorable environment for prevascular-like endothelial organization. Given its modular and self-organizing nature, our strategy may be applied for the fabrication of larger constructs with a highly controlled starting point to be used for local regeneration upon implantation or as drug-screening platforms.

show abstract

Section: Resultsmentioning

confidence: 97%

Bioengineered Hierarchical Bonelike Compartmentalized Microconstructs Using Nanogrooved Microdiscs

Bjørge

Sousa

Patrício

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…Hence, it would be interesting to investigate the role of this miRNA group in response to therapy. The ubiquitin-mediated proteolysis pathway was also enriched in the group of miRNAs associated with MMBD; this pathway seems to have an important role in MMBD due to the reported role of E3 ubiquitin ligase in the regulation of osteoblast differentiation and bone formation [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

A Cancer-Related microRNA Signature Shows Biomarker Utility in Multiple Myeloma

Παπανώτα

Karousi

Kontos

et al. 2021

IJMS

View full text Add to dashboard Cite

Multiple myeloma (MM) is the second most common hematological malignancy, arising from terminally differentiated B cells, namely plasma cells. miRNAs are small non-coding RNAs that participate in the post-transcriptional regulation of gene expression. In this study, we investigated the role of nine miRNAs in MM. CD138+ plasma cells were selected from bone marrow aspirates from MM and smoldering MM (sMM) patients. Total RNA was extracted and in vitro polyadenylated. Next, first-strand cDNA synthesis was performed using an oligo-dT–adapter primer. For the relative quantification of the investigated miRNAs, an in-house real-time quantitative PCR (qPCR) assay was developed. A functional in silico analysis of the miRNAs was also performed. miR-16-5p and miR-155-5p expression was significantly lower in the CD138+ plasma cells of MM patients than in those of sMM patients. Furthermore, lower levels of miR-15a-5p, miR-16-5p, and miR-222-3p were observed in the CD138+ plasma cells of MM patients with osteolytic bone lesions, compared to those without. miR-125b-5p was also overexpressed in the CD138+ plasma cells of MM patients with bone disease that presented with skeletal-related events (SREs). Furthermore, lower levels of miR-223-3p were associated with significantly worse overall survival in MM patients. In conclusion, we propose a miRNA signature with putative clinical utility in MM.

show abstract

“…Ubiquitination is a reversible process regulated by the ubiquitin-proteasome system, which is important for the homeostasis of cells 10 . Deubiquitinating enzymes (DUBs) remove the ubiquitination modification from the target protein and play an important role in the ubiquitin-proteasome system.…”

Section: Introductionmentioning

confidence: 99%

OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF-alpha/NF-kappaB signaling pathways and sensitize ccRCC to TKIs

Li¹,

Yan²,

Yu³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and has the highest mortality rate. For metastatic RCC, systemic drug therapy is the most important method in addition to surgical tumor reduction. In recent years, tyrosine kinase inhibitors (TKIs) targeting the angiogenesis have been applied to treat ccRCC and achieved profound therapeutic effects. It has been reported that most patients receiving antiangiogenic therapy will develop resistance within 15 months. The mechanism of resistance to targeted therapy is extremely complex and has not been clarified. Ovarian tumor-associated protease domain-containing proteins (OTUDs) belonging to DUBs play a critical role in the tumorigenesis of solid tumors. However, the specific role of OTUDs in ccRCC is still elusive. Here, we investigated the clinicopathological role of OTUD family members in ccRCC. We demonstrated that OTUD1 was downregulated in renal cancer and involved in the poor prognosis of renal cancer. Then, we showed that OTUD1 inhibits cancer cell growth. Moreover, analysis of OTUD1 RNA-seq data indicated that OTUD1 inhibition triggers the AKT and NF-kappa B pathways in renal cancer cells. Furthermore, OTUD1 interacts with PTEN and regulates its stability. Subsequently, we revealed that downregulation of OTUD1 contributes to the sensitivity of renal cancer cells to TKIs, and this effect was blocked by TNF/NF-kappa B inhibitors and AKT inhibitors. Thus, we identified that the OTUD1-PTEN axis suppresses tumor growth and regulates the resistance of renal cancer to TKIs.

show abstract

E3 Ubiquitin Ligase-Mediated Regulation of Osteoblast Differentiation and Bone Formation

Cited by 20 publications

References 99 publications

Bioengineered Hierarchical Bonelike Compartmentalized Microconstructs Using Nanogrooved Microdiscs

Bioengineered Hierarchical Bonelike Compartmentalized Microconstructs Using Nanogrooved Microdiscs

A Cancer-Related microRNA Signature Shows Biomarker Utility in Multiple Myeloma

OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF-alpha/NF-kappaB signaling pathways and sensitize ccRCC to TKIs

Contact Info

Product

Resources

About