ArticleReproductive biology and endocrinology : RB&E2012
Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis.
Article in Reproductive biology and endocrinology : RB&E, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Downregulation of Signal Transducer and Activator of Transcription 4 Contributes to Impaired Osteogenic Differentiation of Human Bone Marrow Stem Cells during in vitro Expansion.Cells, tissues, organs · 2026Article
- Comparative Evaluation and Profiling of Chemical Tools for the Nuclear Hormone Receptor Family 2.ACS pharmacology & translational science · 2025Article
- Structures of human TR4LBD-JAZF1 and TR4DBD-DNA complexes reveal the molecular basis of transcriptional regulation.Nucleic acids research · 2023Article
- Scara3 regulates bone marrow mesenchymal stem cell fate switch between osteoblasts and adipocytes by promoting Foxo1.Cell proliferation · 2021Article
- Testicular orphan receptor 4 (TR4) promotes papillary thyroid cancer invasion via activating circ-FNLA/miR-149-5p/MMP9 signaling.Molecular therapy. Nucleic acids · 2021Article
- Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.Journal of cellular and molecular medicine · 2021Article
- Article
- Preclinical studies using miR-32-5p to suppress clear cell renal cell carcinoma metastasis via altering the miR-32-5p/TR4/HGF/Met signaling.International journal of cancer · 2018Article
- RIP140 in monocytes/macrophages regulates osteoclast differentiation and bone homeostasis.JCI insight · 2017Article
- Effect of kidney-reinforcing and marrow-beneficial Chinese medicine on bone metabolism-related factors following spinal cord injury in rats.Experimental and therapeutic medicine · 2016Article
- Bat Accelerated Regions Identify a Bat Forelimb Specific Enhancer in the HoxD Locus.PLoS genetics · 2016Article
- NF-κB Has a Direct Role in Inhibiting Bmp- and Wnt-Induced Matrix Protein Expression.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- TR4 nuclear receptor increases prostate cancer invasion via decreasing the miR-373-3p expression to alter TGFβR2/p-Smad3 signals.Oncotarget · 2015Article
- TR4 Nuclear Receptor Alters the Prostate Cancer CD133+ Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression.Molecular cancer therapeutics · 2015Article
- The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status.Neoplasia (New York, N.Y.) · 2015Article
- TR4 Nuclear Receptor Different Roles in Prostate Cancer Progression.Frontiers in endocrinology · 2015Review
- TR4 nuclear receptor enhances prostate cancer initiation via altering the stem cell population and EMT signals in the PPARG-deleted prostate cells.Oncoscience · 2015Article
- Minireview: Pathophysiological roles of the TR4 nuclear receptor: lessons learned from mice lacking TR4.Molecular endocrinology (Baltimore, Md.) · 2014Article
- The orphan nuclear receptors at their 25-year reunion.Journal of molecular endocrinology · 2013Review
- Recent advances in the study of testicular nuclear receptor 4.Journal of Zhejiang University. Science. B · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundEarly studies suggested that TR4 nuclear receptor might play important roles in the skeletal development, yet its detailed mechanism remains unclear.
methodsWe generated TR4 knockout mice and compared skeletal development with their wild type littermates. Primary bone marrow cells were cultured and we assayed bone differentiation by alkaline phosphatase and alizarin red staining. Primary calvaria were cultured and osteoblastic marker genes were detected by quantitative PCR. Luciferase reporter assays, chromatin immunoprecipitation (ChIP) assays, and electrophoretic mobility shift assays (EMSA) were performed to demonstrate TR4 can directly regulate bone differentiation marker osteocalcin.
resultsWe first found mice lacking TR4 might develop osteoporosis. We then found that osteoblast progenitor cells isolated from bone marrow of TR4 knockout mice displayed reduced osteoblast differentiation capacity and calcification. Osteoblast primary cultures from TR4 knockout mice calvaria also showed higher proliferation rates indicating lower osteoblast differentiation ability in mice after loss of TR4. Mechanism dissection found the expression of osteoblast markers genes, such as ALP, type I collagen alpha 1, osteocalcin, PTH, and PTHR was dramatically reduced in osteoblasts from TR4 knockout mice as compared to those from TR4 wild type mice. In vitro cell line studies with luciferase reporter assay, ChIP assay, and EMSA further demonstrated TR4 could bind directly to the promoter region of osteocalcin gene and induce its gene expression at the transcriptional level in a dose dependent manner.
conclusionsTogether, these results demonstrate TR4 may function as a novel transcriptional factor to play pathophysiological roles in maintaining normal osteoblast activity during the bone development and remodeling, and disruption of TR4 function may result in multiple skeletal abnormalities.
Indexed as
Identifiers
What OpenQuestion holds
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.