TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone

Hiroaki Saito, Andreas Gasser, Simona Bolamperti, Miki Maeda, Levi Matthies, Katharina Jähn, Courtney L. Long, Hartmut Schlüter, Marcel Kwiatkowski, Vaibhav Saini, Paola Divieti Pajevic, Teresita Bellido, Andre J. Wijnen, Khalid S. Mohammad, Theresa A. Guise, Hanna Taipaleenmäki and Eric Hesse ()
Additional contact information
Hiroaki Saito: University Medical Center Hamburg-Eppendorf
Andreas Gasser: University Medical Center Hamburg-Eppendorf
Simona Bolamperti: University Medical Center Hamburg-Eppendorf
Miki Maeda: University Medical Center Hamburg-Eppendorf
Levi Matthies: University Medical Center Hamburg-Eppendorf
Katharina Jähn: University Medical Center Hamburg-Eppendorf
Courtney L. Long: University Medical Center Hamburg-Eppendorf
Hartmut Schlüter: University Medical Center Hamburg-Eppendorf
Marcel Kwiatkowski: University Medical Center Hamburg-Eppendorf
Vaibhav Saini: Massachusetts General Hospital
Paola Divieti Pajevic: Massachusetts General Hospital
Teresita Bellido: Indiana University School of Medicine
Andre J. Wijnen: Mayo Clinic
Khalid S. Mohammad: Indiana School of Medicine
Theresa A. Guise: Indiana School of Medicine
Hanna Taipaleenmäki: University Medical Center Hamburg-Eppendorf
Eric Hesse: University Medical Center Hamburg-Eppendorf

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Osteoporosis is caused by increased bone resorption and decreased bone formation. Intermittent administration of a fragment of Parathyroid hormone (PTH) activates osteoblast-mediated bone formation and is used in patients with severe osteoporosis. However, the mechanisms by which PTH elicits its anabolic effect are not fully elucidated. Here we show that the absence of the homeodomain protein TG-interacting factor 1 (Tgif1) impairs osteoblast differentiation and activity, leading to a reduced bone formation. Deletion of Tgif1 in osteoblasts and osteocytes decreases bone resorption due to an increased secretion of Semaphorin 3E (Sema3E), an osteoclast-inhibiting factor. Tgif1 is a PTH target gene and PTH treatment failed to increase bone formation and bone mass in Tgif1-deficient mice. Thus, our study identifies Tgif1 as a novel regulator of bone remodeling and an essential component of the PTH anabolic action. These insights contribute to a better understanding of bone metabolism and the anabolic function of PTH.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-08778-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08778-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-08778-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().