ArticleCell death & disease2021
A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Protein acylation and bone metabolism: bidirectional crosstalk linking metabolic reprogramming to skeletal homeostasis.Journal of molecular histology · 2026Review
- RUNX2 promotes osteoclast differentiation and bone resorption via the newly identified LncRNA-ROD: implications for alveolar remodeling.International journal of oral science · 2026Article
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- KAT6A regulates osteoclast differentiation and bone resorption through TET1-mediated TRPV4 expression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Decoding Epigenetic Switches: How Histone Acetylation/Deacetylation Regulates Mononuclear/Macrophage Fate in Bone Disorders.International journal of biological sciences · 2026Review
- Insights Into the HIF-1α-Mediated NLRP3 Pyroptosis Pathway in the Regulation of Musculoskeletal Diseases in the High-Altitude Environment.Journal of inflammation research · 2026Review
- Loss of Brd4 alleviates pathological bone loss via Slc9b2 suppression in osteoclastogenesis.Clinical and translational medicine · 2025Article
- NAT10 promotes osteoclastogenesis in inflammatory bone loss by catalyzing Fos mRNA ac4C modification and upregulating MAPK signaling pathway.Journal of advanced research · 2025Article
- Targeting BRD4 to attenuate RANKL-induced osteoclast activation and bone erosion in rheumatoid arthritis.Molecular and cellular biochemistry · 2025Article
- Cbx4 SUMOylates BRD4 to regulate the expression of inflammatory cytokines in post-traumatic osteoarthritis.Experimental & molecular medicine · 2024Article
- Trifolirhizin protects ovariectomy-induced bone loss in mice by inhibiting osteoclast differentiation and bone resorption.Heliyon · 2024Article
- Bazi Bushen capsule attenuates cardiac systolic injury via SIRT3/SOD2 pathway in high-fat diet-fed ovariectomized mice.Heliyon · 2024Article
- Exploring epigenetic strategies for the treatment of osteoporosis.Molecular biology reports · 2024Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- BRD4 facilitates osteogenic differentiation of human bone marrow mesenchymal stem cells through WNT4/NF-κB pathway.Journal of orthopaedic surgery and research · 2023Article
- BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism.Nature communications · 2023Article
- 11β-Hydroxysteroid Dehydrogenase Type 1 Facilitates Osteoporosis by Turning on Osteoclastogenesis through Hippo Signaling.International journal of biological sciences · 2023Article
- Targeted BRD4 protein degradation by dBET1 ameliorates acute ischemic brain injury and improves functional outcomes associated with reduced neuroinflammation and oxidative stress and preservation of blood-brain barrier integrity.Journal of neuroinflammation · 2022Article
- Dietary Collagen Hydrolysates Retard Estrogen Deficiency-Induced Bone Loss through Blocking Osteoclastic Activation and Enhancing Osteoblastic Matrix Mineralization.Biomedicines · 2022Article
- A novel oncogenic seRNA promotes nasopharyngeal carcinoma metastasis.Cell death & disease · 2022Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Bromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F-actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL-stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.
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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.