ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2011
Identification of the homeobox protein Prx1 (MHox, Prrx-1) as a regulator of osterix expression and mediator of tumor necrosis factor α action in osteoblast differentiation.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
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- Single-cell transcriptome profiling reveals the heterogeneity of ossification of the posterior longitudinal ligament (OPLL) and its immune microenvironment.Cell biology and toxicology · 2026Article
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- Regulating osteogenic differentiation of bone marrow mesenchymal stem cells by mTORC1 signaling pathway inhibits bone defect repair in mice.Journal of orthopaedic surgery and research · 2025Article
- Reciprocal negative feedback between Prrx1 and miR-140-3p regulates rapid chondrogenesis in the regenerating antler.Cellular & molecular biology letters · 2024Article
- MicroRNAs-mediated regulation pathways in rheumatic diseases.Inflammopharmacology · 2023Review
- Differential regulation of skeletal stem/progenitor cells in distinct skeletal compartments.Frontiers in physiology · 2023Review
- Diverse stem cells for periodontal tissue formation and regeneration.Genesis (New York, N.Y. : 2000) · 2022Review
- Nanoscale hybrid implant surfaces and Osterix-mediated osseointegration.Journal of biomedical materials research. Part A · 2022Article
- Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment.Chinese herbal medicines · 2021Article
- Molecular mechanisms of intermuscular bone development in fish: a review.Zoological research · 2021Review
- Unveiling diversity of stem cells in dental pulp and apical papilla using mouse genetic models: a literature review.Cell and tissue research · 2021Review
- Association of Antibiotic Alterations in Gut Microbiota With Decreased Osseointegration of an Intramedullary Nail in Mice With and Without Osteomyelitis.Frontiers in endocrinology · 2021Article
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- GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis.International journal of molecular sciences · 2020Article
- Osteoblast-Based Therapy-A New Approach for Bone Repair in Osteoporosis: Pre-Clinical Setting.Tissue engineering and regenerative medicine · 2020Article
- Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials.Journal of clinical medicine · 2020Review
- PRRX1-induced epithelial-to-mesenchymal transition in salivary adenoid cystic carcinoma activates the metabolic reprogramming of free fatty acids to promote invasion and metastasis.Cell proliferation · 2020Article
- Site-Specific Load-Induced Expansion of Sca-1JBMR plus · 2019Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor α (TNF-α) promotes bone loss and inhibits bone formation. Osterix (Osx, SP7) is a transcription factor required for osteoblast (OB) differentiation because deletion results in a cartilaginous skeleton. We previously described a TNF suppressor element in the Osx promoter that was used to isolate nuclear proteins mediating TNF inhibition of OB differentiation. Nuclear extracts from TNF-treated pre-OBs were incubated with the TNF suppressor element for protein pull-down, and tryptic fragments were analyzed by mass spectrometry. Chromatin immunoprecipitation (ChIP) assay confirmed eight bound transcription factors. One protein, the paired related homeobox protein (Prx1), had been shown previously to have a critical role in limb bud formation and skeletal patterning. PCR revealed Prx1 expression in primary stromal cells (MSCs), C3H10T1/2 cells, and MC3T3 preosteoblasts. TNF stimulated a 14-fold increase in mRNA for Prx1, rapid cell accumulation in MC3T3 cells, and expression in periosteal and trabecular lining cells in vivo. Transient expression of Prx inhibited transcription of Osx and RUNX2. Expression of the Prx1b isoform or Prx2 decreased Osx and RUNX2 mRNA and OB differentiation in preosteoblasts. Silencing of Prx1 with siRNA abrogated TNF suppression of Osx mRNA and increased basal Osx expression. Electrophoretic mobility shift revealed Prx1b as the preferred isoform binding the Osx promoter. These results identify the homeobox protein Prx1 as an obligate mediator of TNF inhibition of Osx and differentiation of OB progenitors. Activation of Prx1 by TNF may contribute to reduced bone formation in inflammatory arthritis, menopause, and aging.
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