ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2015
N-cadherin restrains PTH activation of Lrp6/β-catenin signaling and osteoanabolic action.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 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
23 citing papers in PubMed, 46 citations in OpenAlex.
- Effects and mechanisms of iron overload on the proliferation and differentiation of preosteoblastic cellsFrontiers in bioengineering and biotechnology · 2026Article
- Differential bone and vessel type formation at superior and dura periosteum during cranial bone defect repair.Bone research · 2025Article
- Fracture healing: cellular mechanisms and impact of parathyroid hormone and its analogs.Frontiers in endocrinology · 2025Review
- Knockouts ofiScience · 2024Article
- Review
- Connexin43 in mesenchymal lineage cells regulates body adiposity and energy metabolism in mice.JCI insight · 2024Article
- Connexin43 in mesenchymal lineage cells regulates body adiposity and energy metabolism in mice.bioRxiv : the preprint server for biology · 2024Article
- NACA and LRP6 Are Part of a Common Genetic Pathway Necessary for Full Anabolic Response to Intermittent PTH.International journal of molecular sciences · 2022Article
- Anabolic actions of PTH in murine models: two decades of insights.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Wnt/β-catenin pathway and cell adhesion deregulation in CSDE1-related intellectual disability and autism spectrum disorders.Molecular psychiatry · 2021Article
- N-cadherin in osteolineage cells modulates stromal support of tumor growth.Journal of bone oncology · 2021Article
- Article
- Parathyroid hormone increases alveolar bone homoeostasis during orthodontic tooth movement in rats with periodontitis via crosstalk between STAT3 and β-catenin.International journal of oral science · 2020Article
- Alcohol-induced Wnt signaling inhibition during bone fracture healing is normalized by intermittent parathyroid hormone treatment.Animal models and experimental medicine · 2020Article
- Local delivery of a novel PTHrPRSC advances · 2018Article
- Oxidized phospholipids are ligands for LRP6.Bone research · 2018Article
- Ixazomib enhances parathyroid hormone-induced β-catenin/T-cell factor signaling by dissociating β-catenin from the parathyroid hormone receptor.Molecular biology of the cell · 2017Article
- N-cadherin Regulation of Bone Growth and Homeostasis Is Osteolineage Stage-Specific.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation.Bone & joint research · 2017Article
- Adult-Onset Deletion of β-Catenin in (10kb)Dmp1-Expressing Cells Prevents Intermittent PTH-Induced Bone Gain.Endocrinology · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Interaction between parathyroid hormone/parathyroid hormone-related peptide receptor 1 (PTHR1) and low-density lipoprotein receptor-related protein 6 (Lrp6) is important for parathyroid hormone (PTH) signaling and anabolic action. Because N-cadherin has been shown to negatively regulate canonical Wnt/β-catenin signaling, we asked whether N-cadherin alters PTH signaling and stimulation of bone formation. Ablation of the N-cadherin gene (Cdh2) in primary osteogenic lineage cells resulted in increased Lrp6/PTHR1 interaction in response to PTH1-34 , associated with enhanced PTH-induced PKA signaling and PKA-dependent β-catenin C-terminus phosphorylation, which promotes β-catenin transcriptional activity. β-catenin C-terminus phosphorylation was abolished by Lrp6 knockdown. Accordingly, PTH1-34 stimulation of Tcf/Lef target genes, Lef1 and Axin2, was also significantly enhanced in Cdh2-deficient cells. This enhanced responsiveness to PTH extends to the osteo-anabolic effect of PTH, as mice with a conditional Cdh2 deletion in Osx+ cells treated with intermittent doses of PTH1-34 exhibited significantly larger gains in trabecular bone mass relative to control mice, the result of accentuated osteoblast activity. Therefore, N-cadherin modulates Lrp6/PTHR1 interaction, restraining the intensity of PTH-induced β-catenin signaling, and ultimately influencing bone formation in response to intermittent PTH administration.
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.