ArticleMolecules and cells2011
Hypoxia inducible factor-1α directly induces the expression of receptor activator of nuclear factor-κB ligand in periodontal ligament fibroblasts.
Article in Molecules and cells, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- MMPs at Work: Deciphering Their Role in the Cellular Mechanisms of Orthodontic Tooth Movement.International journal of molecular sciences · 2026Review
- Hypoxia-Inducible Factors in Rheumatoid Arthritis: Central Pathogenic Roles and Therapeutic Opportunities.Journal of inflammation research · 2026Review
- The effects of systemic and sustained hypoxia on orthodontic tooth movement in rats.Scientific reports · 2025Article
- Characterization of a periodontal-inflammatory microRNA profile during multibracket orthodontic treatment in adolescents.Scientific reports · 2025Article
- Gingiva Mesenchymal Stem Cells Normoxic or Hypoxic Preconditioned Application Under Orthodontic Mechanical Force on Osterix, Osteopontin, and ALP Expression.European journal of dentistry · 2024Article
- Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain, big gain.Frontiers in pain research (Lausanne, Switzerland) · 2024Review
- Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.Journal of experimental & clinical cancer research : CR · 2023Review
- ANGPTL4 regulates the osteogenic differentiation of periodontal ligament stem cells.Functional & integrative genomics · 2022Article
- Article
- Pulpal outcomes in orthodontic tooth movement in diabetes mellitus.Odontology · 2021Article
- Role of nitric oxide in orthodontic tooth movement (Review).International journal of molecular medicine · 2021Review
- Ligament/Tendon Culture under Hypoxic Conditions: A Systematic Review.Advanced pharmaceutical bulletin · 2021Review
- Interleukin-20 Acts as a Promotor of Osteoclastogenesis and Orthodontic Tooth Movement.Stem cells international · 2021Article
- Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2.Gene: X · 2020Article
- Osteoblast-Osteoclast Coculture Amplifies Inhibitory Effects of FG-4592 on Human Osteoclastogenesis and Reduces Bone Resorption.JBMR plus · 2020Article
- Asperosaponin VI Injection Enhances Orthodontic Tooth Movement in Rats.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Do electrical current and laser therapies improve bone remodeling during an orthodontic treatment with corticotomy?Clinical oral investigations · 2019Article
- Transcriptional activation of glucose transporter 1 in orthodontic tooth movement-associated mechanical response.International journal of oral science · 2018Article
- Orthodontic tooth movement: The biology and clinical implications.The Kaohsiung journal of medical sciences · 2018Review
- Hypoxia-regulated human periodontal ligament cells via Wnt/β-catenin signaling pathway.Medicine · 2017Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During orthodontic tooth movement, local hypoxia and enhanced osteoclastogenesis are observed in the compression side of periodontal tissues. The receptor activator of nuclear factor-κB ligand (RANKL) is an osteoblast/stromal cell-derived factor that is essential for osteoclastogenesis. In this study, we examined the effect of hypoxia on RANKL expression in human periodontal ligament fibroblasts (PDLFs) to investigate the relationship between local hypoxia and enhanced osteoclastogenesis in the compression side of periodontal tissues. Hypoxia significantly enhanced the levels of RANKL mRNA and protein as well as hypoxia inducible factor-1α (HIF-1α) protein in PDLFs. Constitutively active HIF-1α alone significantly increased the levels of RANKL expression in PDLFs under normoxic conditions, whereas dominant negative HIF-1α blocked hypoxia-induced RANKL expression. To investigate further whether HIF-1α directly regulates RANKL transcription, a luciferase reporter assay was performed using the reporter vector containing the RANKL promoter sequence. Exposure to hypoxia or overexpression of constitutively active HIF-1α significantly increased RANKL promoter activity, whereas dominant negative HIF-1α blocked hypoxia-induced RANKL promoter activity. Furthermore, mutations of putative HIF-1α binding elements in RANKL promoter prevented hypoxia-induced RANKL promoter activity. The results of chromatin immunoprecipitation showed that hypoxia or constitutively active HIF-1α increased the DNA binding of HIF-1α to RANKL promoter. These results suggest that HIF-1α mediates hypoxia-induced up-regulation of RANKL expression and that in compression side periodontal ligament, hypoxia enhances osteoclastogenesis, at least in part, via an increased RANKL expression in PDLFs.
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