ArticleExperimental cell research2009
Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-alpha with BCAR1 and Traf6.
Article in Experimental cell research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 91 citations in OpenAlex.
- Estradiol regulates osteoclast sialylation via ST3Gal1 in postmenopausal osteoporosis.Bone research · 2026Article
- Sex- and age-specific musculoskeletal adverse events of isotretinoin: disproportionality analysis of the FAERS database combined with a clinical case series.Frontiers in pharmacology · 2026Article
- Dietary fiber derived short-chain fatty acids as a critical driver of the gut-bone axis in animal bone health: A review.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Review
- A comprehensive review and advanced biomolecule-based therapies for osteoporosis.Journal of advanced research · 2025Review
- Nrf2 Activation as a Therapeutic Target for Flavonoids in Aging-Related Osteoporosis.Nutrients · 2025Review
- Bone-organ axes: bidirectional crosstalk.Military Medical Research · 2024Review
- Bone equilibria and disruptions.Journal of the Pediatric Orthopaedic Society of North America · 2024Article
- Pyroptosis mediates osteoporosis via the inflammation immune microenvironment.Frontiers in immunology · 2024Review
- Managing Early Onset Osteoporosis: The Impact of Premature Ovarian Insufficiency on Bone Health.Journal of clinical medicine · 2023Review
- Modulation of bone remodeling by the gut microbiota: a new therapy for osteoporosis.Bone research · 2023Review
- HTRA1 from OVX rat osteoclasts causes detrimental effects on endplate chondrocytes through NF-κB.Heliyon · 2023Article
- Review
- Article
- The role and regulation mechanism of Chinese traditional fitness exercises on the bone and cartilage tissue in patients with osteoporosis: A narrative review.Frontiers in physiology · 2023Review
- Review on the protective activity of osthole against the pathogenesis of osteoporosis.Frontiers in pharmacology · 2023Review
- ECSIT is essential for RANKL-induced stimulation of mitochondria in osteoclasts and a target for the anti-osteoclastogenic effects of estrogens.Frontiers in endocrinology · 2023Article
- Circulating liver function markers and the risk of COPD in the UK Biobank.Frontiers in endocrinology · 2023Article
- Effects of Loganin on Bone Formation and Resorption In Vitro and In Vivo.International journal of molecular sciences · 2022Article
- Biological Deciphering of the "Kidney Governing Bones" Theory in Traditional Chinese Medicine.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- The Effects of Osteoporotic and Non-osteoporotic Medications on Fracture Risk and Bone Mineral Density.Drugs · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The effects of estrogen on osteoclast survival and differentiation were studied using CD14-selected mononuclear osteoclast precursors from peripheral blood. Estradiol at approximately 1 nM reduced RANKL-dependent osteoclast differentiation by 40-50%. Osteoclast differentiation was suppressed 14 days after addition of RANKL even when estradiol was withdrawn after 18 h. In CD14+ cells apoptosis was rare and was not augmented by RANKL or by 17-beta-estradiol. Estrogen receptor-alpha (ERalpha) expression was strongly down-regulated by RANKL, whether or not estradiol was present. Mature human osteoclasts thus cannot respond to estrogen via ERalpha. However, ERalpha was present in CD14+ osteoclast progenitors, and a scaffolding protein, BCAR1, which binds ERalpha in the presence of estrogen, was abundant. Immunoprecipitation showed rapid (approximately 5 min) estrogen-dependent formation of ERalpha-BCAR1 complexes, which were increased by RANKL co-treatment. The RANKL-signaling intermediate Traf6, which regulates NF-kappaB activity, precipitated with this complex. Reduction of NF-kappaB nuclear localization occurred within 30 min of RANKL stimulation, and estradiol inhibited the phosphorylation of IkappaB in response to RANKL. Inhibition by estradiol was abolished by siRNA knockdown of BCAR1. We conclude that estrogen directly, but only partially, curtails human osteoclast formation. This effect requires BCAR1 and involves a non-genomic interaction with ERalpha.
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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.