ArticleScientific reports2017
Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting of Itch by clomipramine or gene therapy improves cognitive defects related to Alzheimer's disease.iScience · 2026Article
- The novel organoselenium compound 4aa ameliorates osteoporosis by modulating gut microbiota composition and fecal metabolite profiles.Frontiers in endocrinology · 2025Article
- 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
- Bisphosphonate-incorporated coatings for orthopedic implants functionalization.Materials today. Bio · 2023Review
- Zoledronic Acid Implant Coating Results in Local Medullary Bone Growth.Molecular pharmaceutics · 2022Article
- 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
- Bone-Targeted Bortezomib Inhibits Bortezomib-Resistant Multiple Myeloma in Mice by Providing Higher Levels of Bortezomib in Bone.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Zoledronic acid inhibits osteoclastogenesis and bone resorptive function by suppressing RANKL‑mediated NF‑κB and JNK and their downstream signalling pathways.Molecular medicine reports · 2022Article
- E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration.Stem cells international · 2022Review
- Specific overexpression of SIRT1 in mesenchymal stem cells rescues hematopoiesis niche in BMI1 knockout mice through promoting CXCL12 expression.International journal of biological sciences · 2022Article
- The E3 ubiquitin ligase Itch limits the progression of post-traumatic osteoarthritis in mice by inhibiting macrophage polarization.Osteoarthritis and cartilage · 2021Article
- Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review.BMC cancer · 2020Review
- Selective serotonin reuptake inhibitors (SSRI) affect murine bone lineage cells.Life sciences · 2020Article
- 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
- Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in Mice.Pharmaceutics · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Patients taking antidepressants, including Clomipramine (CLP), have an increased risk of osteoporotic fracture. However, the effects of CLP on bone metabolism are unknown. Here, we demonstrate that WT mice treated with CLP for 2 weeks had significantly reduced trabecular bone volume and cortical bone thickness, associated with increased osteoclast (OC) numbers, but had no change in osteoblast numbers or bone formation rate. Bone marrow cells from CLP-treated mice had normal OC precursor frequency, but formed significantly more OCs when they were cultured with RANKL and M-CSF. CLP promoted OC formation and bone resorption and expression of OC-associated genes. CLP-induced bone loss was prevented by Zoledronic acid. At the molecular level, CLP inhibited the activity of the ubiquitin E3 ligase Itch. CLP did not promote OC formation from bone marrow cells of Itch-/- mice in vitro nor induce bone loss in Itch-/- mice. Our findings indicate that CLP causes bone loss by enhancing Itch-mediated osteoclastogenesis, which was prevented by Zoledronic acid. Thus, anti-resorptive therapy could be used to prevent bone loss in patients taking antidepressants, such as CLP.
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Registered trials
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.