ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2012
Premature T cell senescence in Ovx mice is inhibited by repletion of estrogen and medicarpin: a possible mechanism for alleviating bone loss.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- The role of CD8Frontiers in immunology · 2026Pooled it
- CD4Combinatorial chemistry & high throughput screening · 2026Article
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- Microbially-Induced Exosomes from Dendritic Cells Promote Paracrine Immune Senescence: Novel Mechanism of Bone Degenerative Disease in Mice.Aging and disease · 2023Article
- Senescent CD4International journal of molecular sciences · 2022Review
- Cellular senescence in musculoskeletal homeostasis, diseases, and regeneration.Bone research · 2021Review
- Premature Senescence of T-cells Favors Bone Loss During Osteolytic Diseases. A New Concern in the Osteoimmunology Arena.Aging and disease · 2021Article
- Increased systemic inflammation and altered distribution of T-cell subsets in postmenopausal women.PloS one · 2020Article
- Targeting Cell Senescence for the Treatment of Age-Related Bone Loss.Current osteoporosis reports · 2019Review
- Bu‑Shen‑Ning‑Xin decoction suppresses osteoclastogenesis by modulating RANKL/OPG imbalance in the CD4+ T lymphocytes of ovariectomized mice.International journal of molecular medicine · 2018Article
- From Osteoimmunology to Osteomicrobiology: How the Microbiota and the Immune System Regulate Bone.Calcified tissue international · 2018Review
- Bone Remodeling and the Microbiome.Cold Spring Harbor perspectives in medicine · 2018Review
- Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene.The Journal of biological chemistry · 2017Article
- IL-18BP is decreased in osteoporotic women: Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation.Scientific reports · 2016Article
- Identification of GRP78 as a molecular target of medicarpin in osteoblast cells by proteomics.Molecular and cellular biochemistry · 2016Article
- Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics.The Journal of clinical investigation · 2016Article
- Bu-Shen-Ning-Xin Decoction ameliorated the osteoporotic phenotype of ovariectomized mice without affecting the serum estrogen concentration or uterus.Drug design, development and therapy · 2015Article
- Bu-Shen-Ning-Xin decoction: inhibition of osteoclastogenesis by abrogation of the RANKL-induced NFATc1 and NF-κB signaling pathways via selective estrogen receptor α.Drug design, development and therapy · 2015Article
- Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential.Steroids · 2014Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledPresently the relationship between CD28, biological marker of senescence, and ovariectomy is not well understood. We show that ovariectomy leads to CD28 loss on T cells and estrogen (E2) repletion and medicarpin (Med) inhibits this effect. We thus propose that Med/E2 prevents bone loss by delaying premature T cell senescence.
introductionEstrogen deficiency triggers reproductive aging by accelerating the amplification of TNF-α-producing T cells, thereby leading to bone loss. To date, no study has been carried out to explain the relationship between CD4(+)CD28null T cells and ovariectomy or osteoporosis. We aim to determine the effect of Ovx on CD28 expression on T cells and effects of E2 and medicarpin (a pterocarpan phytoalexin) with proven osteoprotective effect on altered T cell responses.
methodsAdult, female Balb/c mice were taken for the study. The groups were: sham, Ovx, Ovx + Med or E2. Treatments were given daily by oral gavage. At autopsy bone marrow and spleen were flushed out and cells labelled with antibodies for FACS analysis. Serum was collected for ELISA.
resultsIn Ovx mice, Med/E2 at their respective osteoprotective doses resulted in thymus involution and lowered Ovx-induced increase in serum TNF-α level and its mRNA levels in the BM T cells. Med/E2 reduced BM and spleen CD4(+) T cell proliferation and prevented CD28 loss on CD4(+) T cells. Further, Med abrogated TNF-α-induced loss of CD28 expression in the BM T cells.
conclusionsTo our knowledge this is the first report to determine the mechanism of CD28 loss on T cells as a result of ovariectomy. Our study demonstrates that Ovx leads to the generation of premature senescent CD4(+)CD28null T cells, an effect inhibited by E2 and Med. We propose that one of the mechanisms by which Med/E2 alleviates Ovx-induced bone loss is by delaying T cell senescence and enhancing CD28 expression.
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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.