Evidence map›Paper›PMID 28676438›Full record

ArticleBone2017

Parathyroid hormone inhibits Notch signaling in osteoblasts and osteocytes.

Stefano Zanotti, Ernesto Canalis

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed.

  1. Article
  2. Role of Notch signaling in corticalization.Journal of endocrinological investigation · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Anabolic therapy for osteoporosis: update on efficacy and safety.Archives of endocrinology and metabolism · 2022
    Review
  9. Article
  10. 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 · 2022
    Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Antisense oligonucleotides targetingThe Journal of biological chemistry · 2020
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Stefano ZanottiDepartments of Orthopaedic Surgery and Medicine, UConn Musculoskeletal Institute, UConn Health, Farmington, CT 06030-5456, USA. Electronic address: zanotti@uchc.edu.
Ernesto CanalisDepartments of Orthopaedic Surgery and Medicine, UConn Musculoskeletal Institute, UConn Health, Farmington, CT 06030-5456, USA.

Funding

Mechanisms of Notch Action in BoneR01DK045227 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI CANALIS, ERNESTO · 1991 to 2018
$4.7M
Role of NFAT in the SkeletonR01AR068160 · NIAMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI CANALIS, ERNESTO · 2015 to 2019
$2.0M
Role of Notch Signaling in OsteocytesR01AR063049 · NIAMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI CANALIS, ERNESTO · 2013 to 2017
$1.8M
NIAMS NIH HHS R01 AR063049NIAMS NIH HHS R01 AR068160NIDDK NIH HHS R01 DK045227
6 · The paper itself

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.

Indexed as

AnimalsMaleMiceMice, Inbred C57BLOsteoblastsOsteocytesParathyroid HormoneReceptors, NotchSignal TransductionParathyroid HormoneReceptors, NotchNotchOsteoblastOsteocytePTHRbpjκ

Identifiers

PMID28676438
PMCPMC5568480

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Registered trials

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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.