ArticleBone2017
Parathyroid hormone inhibits Notch signaling in osteoblasts and osteocytes.
Article in Bone, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- NOTCH3 disrupts the osteoblast transcriptome in femoral bone of 1-month-old male C57BL/6 mice.Bone · 2026Article
- Role of Notch signaling in corticalization.Journal of endocrinological investigation · 2026Review
- Article
- Article
- MiRNA-mRNA network in osteoporotic fractures proposes the functional mechanism of hsa-miR-32-3p/TNFSF11 axis.Journal of orthopaedic surgery and research · 2025Article
- Review
- Article
- Anabolic therapy for osteoporosis: update on efficacy and safety.Archives of endocrinology and metabolism · 2022Review
- Article
- The Notch pathway regulates the bone gain induced by PTH anabolic signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Article
- The Interaction Between Intracellular Energy Metabolism and Signaling Pathways During Osteogenesis.Frontiers in molecular biosciences · 2021Review
- 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
- Review
- Antisense oligonucleotides targetingThe Journal of biological chemistry · 2020Article
- Ex Vivo Organ Cultures as Models to Study Bone Biology.JBMR plus · 2020Review
- Different effects of Wnt/β-catenin activation and PTH activation in adult and aged male mice metaphyseal fracture healing.BMC musculoskeletal disorders · 2020Article
- The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases.Frontiers in endocrinology · 2020Review
- An antibody to Notch3 reverses the skeletal phenotype of lateral meningocele syndrome in male mice.Journal of cellular physiology · 2020Article
- The Skeleton of Lateral Meningocele Syndrome.Frontiers in genetics · 2020Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Parathyroid hormone (PTH) and Notch receptors regulate bone formation by governing the function of osteoblastic cells. To determine whether PTH interacts with Notch signaling as a way to control osteoblast function, we tested the effects of PTH on Notch activity in osteoblast- and osteocyte-enriched cultures. Notch signaling was activated in osteoblast-enriched cells from wild-type C57BL/6J mice following exposure to the Notch ligand Delta-like (Dll)1 or by the transient transfection of the Notch intracellular domain (NICD), the transcriptionally active fragment of Notch1. To induce Notch signaling in osteocyte-enriched cultures, a murine model of Notch2 gain-of-function was used. PTH opposed the stimulatory effects of Dll1 on Hey1, Hey2 and HeyL mRNA levels in osteoblast-enriched cells and suppressed the expression of selected Notch target genes in osteocyte-enriched cultures, either under basal conditions or in the context of Notch2 gain-of-function. Induction of Notch signaling in osteocytes did not alter the inhibitory effect of PTH on Sost expression, but reduced the stimulation of Tnfsf11 mRNA levels by PTH. In agreement with these in vitro observations, male mice administered with PTH displayed suppressed Hey1 and HeyL expression in parietal bones. Transactivation experiments with a Notch reporter construct and electrophoretic mobility shift assays in osteoblast-enriched cells suggest that PTH acts by decreasing the capacity of Rbpjκ to bind to DNA. In conclusion, downregulation of Notch in osteoblasts and osteocytes may represent a mechanism contributing to the anabolic effects of PTH in bone.
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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.