Ubiquitin E3 ligase Itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins

Liu, J.; Li, X.; Zhang, H.; Gu, Rong; Wang, Z.; Gao, Zijun; Xing, Lianping

doi:10.1302/2046-3758.63.bjr-2016-0237.r1

Cited by 28 publications

(29 citation statements)

References 30 publications

(43 reference statements)

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“…HERC4 belongs to the HERC family of ubiquitin ligases and encodes HECT and RLD domain containing E3 ubiquitin protein ligase 4 . A recent mouse study demonstrated that ubiquitin E3 ligases, involved in protein degradation, regulate osteoblast function . Therefore, it is plausible that HERC4 might be also important in the pathophysiology of ONJ.…”

Section: Discussionsupporting

confidence: 78%

SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis

Yang

Hamadeh

Katz

et al. 2017

Journal of Bone and Mineral Research

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Osteonecrosis of the jaw (ONJ) is a rare, but serious drug side effect, mainly associated with the use of intravenous (iv) bisphosphonates (BPs). The purpose of this study was to identify genetic variants associated with ONJ in patients of European ancestry treated with iv BPs using whole-exome sequencing (WES). The WES phase 1 included 44 multiple myeloma patients (22 ONJ cases and 22 controls) and WES phase 2 included 17 ONJ patients with solid tumors. Multivariable logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and principal components for ancestry. Meta-analysis of WES phase 1 and 2 was performed to estimate the combined ORs. In silico analyses were then performed to identify expression quantitative loci (eQTL) single-nucleotide polymorphisms (SNPs) that are in high linkage disequilibrium (LD) with the top SNPs. The associations of the potentially functional SNPs were replicated and validated in an independent case-control study of 48 patients of European ancestry treated with iv BPs (19 ONJ cases and 29 controls). The top SNPs in the exome-wide association meta-analysis were two SNPs on chromosome 10: SIRT1 SNP rs7896005 and HERC4 SNP rs3758392 with identical OR of 0.07 (0.01-0.46; p ¼ 3.83 Â 10 À5). In the in silico functional analyses, two promoter region SNPs (rs7894483 and rs3758391) were identified to be in high LD with the index SNPs and are eQTLs for SIRT1 gene in whole blood in the GTEx database. The ORs were 0.30 (0.10-0.88), 0.26 (0.12-0.55), and 0.26 (0.12-0.55) for the WES top SNP rs7896005 and two promoter SNPs rs7894483 and rs3758391, respectively, in the replication sample. In summary, we identified the SIRT1/HERC4 locus on chromosome 10 to be associated with iv BP-induced ONJ and two promoter SNPs that might be the potential genetic markers for this association.

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Section: Discussionsupporting

confidence: 78%

SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis

Yang

Hamadeh

Katz

et al. 2017

Journal of Bone and Mineral Research

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“…Proteins common to bone and other biomineralization systems found in the inner ear of adult black bream ( Acanthopagrus butcheri , n = 3) . In addition to structural collagens and proteoglycans, we also found proteins that are associated with osteoblast function or otherwise act as substrates for extracellular matrix formation .…”

Section: Discussionmentioning

confidence: 80%

“…In addition to the 'usual' otolith proteins, we found high abundances of bone and cartilage type proteoglycans (Mimecan (Osteoglycin), Epiphycan, Biglycan, Decorin, Aggrecan), Collagen types I and II, and osteoblast regulating proteins (e.g. E3 ligase itchy-like) [11, [49][50][51][52]. Importantly, we found no evidence of protein markers for osteoclastic function.…”

Section: Introductionmentioning

confidence: 76%

“…Proteins common to bone and other biomineralization systems found in the inner ear of adult black bream (Acanthopagrus butcheri, n = 3) [11,12,49,50]. In addition to structural collagens and proteoglycans, we also found proteins that are associated with osteoblast function or otherwise act as substrates for extracellular matrix formation [52,75,76,81]. acid (mRNA)-purified, converted to cDNA and prepared for sequencing as per the Low Sample protocol, Illumina Ò TruSeq Ò RNA Sample Preparation v2 Guide.…”

Section: Transcriptome Sequencing Assembly and Annotationmentioning

confidence: 86%

“…Interestingly, while we found an abundance of osteoblast-associated proteins (e.g. E3 ligase itchylike, Collagen triple helix repeat-containing protein 1 [52,75,76]), we found no typical markers of osteoclast activity such as Carbonic anhydrase 2, Cathepsin K, Calcitonin receptor, Cell surface aminopeptidase N/ CD13 or Integrin b3 [77]. Cathepsin K, particularly, is abundantly expressed by osteoclasts [78].…”

Section: Otoliths Are Like Bones But Inertmentioning

confidence: 96%

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The inner ear proteome of fish

et al. 2018

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The mechanisms that underpin the formation, growth and composition of otoliths, the biomineralized stones in the inner ear of fish, are largely unknown, as only a few fish inner ear proteins have been reported. Using a partial transcriptome for the inner ear of black bream (Acanthopagrus butcheri), in conjunction with proteomic data, we discovered hundreds of previously unknown proteins in the otolith. This allowed us to develop hypotheses to explain the mechanisms of inorganic material supply and daily formation of growth bands. We further identified a likely protein mediator of crystal nucleation and an explanation for the apparent metabolic inertness of the otolith. Due to the formation of both daily and annual increments, otoliths are routinely employed as natural chronometers, being used for age and growth estimation, fisheries stock assessments, and the reconstruction of habitat use, movement, diet and the impacts of climate change. Our findings provide an unprecedented view of otolith molecular machinery, aiding in the interpretation of these essential archived data.

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Koumine inhibits RANKL‐induced ubiquitination and NF‐κB activation to prevent ovariectomy and aging‐induced bone loss

You,

Xu,

Zhang

et al. 2023

J of Cellular Biochemistry

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Osteoporosis (OP) is a bone remodeling disease characterized by an imbalance between bone resorption and formation. Osteoclasts are the primary therapeutic targets for treating bone destruction. Koumine (KM), the most bioactive component in Gelsemium alkaloids, exhibits antitumor, immunosuppressive, anti‐inflammatory, and analgesic properties. However, the effects of bone loss have not been well studied. This study conducted in vitro and in vivo verification experiments on KM. The results showed that KM inhibited bone resorption and tartrate‐resistant acid phosphatase positive (TRAP+) osteoclasts development by mature osteoclasts in a dose‐dependent manner. Moreover, KM prevented OVX‐induced OP in vivo and potentially inhibited ubiquitination, a process closely related to various biological activities, including protein interaction, transcription, and transmembrane signal transduction regulation, especially within the nuclear factor‐κB (NF‐κB) pathway. Previous studies have demonstrated that several proteins ubiquitination promotes osteoclastogenesis, our study indicated that KM inhibits early NF‐κB activation and receptor activator of NF‐κB ligand induced ubiquitination, a critical factor in osteoclast differentiation. In conclusion, our research suggests that KM holds potential as an effective therapeutic agent for OP.

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Ubiquitin E3 ligase Itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins

Cited by 28 publications

References 30 publications

SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis

SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis

The inner ear proteome of fish

Koumine inhibits RANKL‐induced ubiquitination and NF‐κB activation to prevent ovariectomy and aging‐induced bone loss

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