ArticleStem cells (Dayton, Ohio)2013
Ubiquitin e3 ligase itch negatively regulates osteoblast differentiation from mesenchymal progenitor cells.
Article in Stem cells (Dayton, Ohio), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- NEDD4 family E3 ligases in osteoporosis: mechanisms and emerging potential therapeutic targets.Journal of orthopaedic surgery and research · 2025Review
- Role of ubiquitination in the occurrence and development of osteoporosis (Review).International journal of molecular medicine · 2024Review
- E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders.Frontiers in cell and developmental biology · 2024Review
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- Molecular Mechanism of Long Noncoding RNA SNHG14 in Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells through the NEDD4L/FOXA2/PCP4 Axis.Stem cells international · 2023Article
- NEDD4 E3 Ligases: Functions and Mechanisms in Bone and Tooth.International journal of molecular sciences · 2022Review
- Silencing Itch in human peripheral blood monocytes promotes their differentiation into osteoclasts.Molecular biology reports · 2022Article
- Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice.PloS one · 2022Article
- E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration.Stem cells international · 2022Review
- The E3 ubiquitin ligase Itch limits the progression of post-traumatic osteoarthritis in mice by inhibiting macrophage polarization.Osteoarthritis and cartilage · 2021Article
- The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis.Translational cancer research · 2021Article
- E3 Ubiquitin Ligase-Mediated Regulation of Osteoblast Differentiation and Bone Formation.Frontiers in cell and developmental biology · 2021Review
- Delivery of RNAi-Based Therapeutics for Bone Regeneration.Current osteoporosis reports · 2020Review
- Targeting Bortezomib to Bone Increases Its Bone Anabolic Activity and Reduces Systemic Adverse Effects in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- B cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation.Nature communications · 2018Article
- Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- Increased PLEKHO1 within osteoblasts suppresses Smad-dependent BMP signaling to inhibit bone formation during aging.Aging cell · 2017Article
- Ubiquitin E3 ligase Itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins.Bone & joint research · 2017Article
- Surgically‑induced mouse models in the study of bone regeneration: Current models and future directions (Review).Molecular medicine reports · 2017Review
- E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration.Frontiers in molecular neuroscience · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Itch, a HECT family E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of target proteins. However, the role of Itch in osteoblasts has not been investigated. We report that Itch(-/-) mice have significantly increased bone volume, osteoblast numbers, and bone formation rate. Using bone marrow stromal cells from Itch(-/-) mice and wild-type (WT) littermates as bone marrow mesenchymal precursor cells (BM-MPCs), we found that BM-MPCs from Itch(-/-) mice have compatible numbers of cells expressing mesenchymal stem cell markers. However, Itch(-/-) BM-MPCs grew faster in an in vitro culture, formed more CFU-F mesenchymal colonies, and exhibited increased osteoblast differentiation and decreased adipogenesis. Importantly, Itch(-/-) mesenchymal colony cells formed significantly more new bone in a tibial defect of recipient mice compared with WT cells. The expression levels of JunB, an AP-1 transcription factor that positively regulate osteoblast differentiation, were significantly increased in Itch(-/-) BM-MPCs when proteasome function is intact. In contrast, the amount of ubiquitinated JunB protein was markedly decreased in Itch(-/-) cells when proteasome function was blocked. Overexpression of WT Itch, but not an Itch ligase-inactive mutant, rescued differentiation defects of Itch(-/-) BM-MPCs. Itch(-/-) BM-MPCs had a similar role in immune modulation as WT cells. Thus, Itch negatively controls osteoblast differentiation from BM-MPCs through the regulation of proteasomal degradation of positive osteoblast regulator JunB protein. Itch is a potential new target for bone anabolic drug development to treat patients with bone loss.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.