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Nat Commun. 2019 Mar 22;10(1):1354. doi: 10.1038/s41467-019-08778-x.

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

Author information

1
Molecular Skeletal Biology Laboratory, Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246, Hamburg, Germany.
2
Mass Spectrometric Proteomics Laboratory, Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246, Hamburg, Germany.
3
Endocrine Unit, Massachusetts General Hospital, 55 Fruit St., Boston, MA, 02114, USA.
4
Department of Molecular and Cell Biology, Boston University, School of Dental Medicine, 72 East Concord St., Boston, MA, 02118, USA.
5
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN, 46202, USA.
6
Department of Orthopedic Surgery, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.
7
Division of Endocrinology, Department of Medicine, Indiana School of Medicine, 545 Barnhill Dr., Indianapolis, IN, 46202, USA.
8
Molecular Skeletal Biology Laboratory, Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246, Hamburg, Germany. e.hesse@uke.de.
9
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN, 46202, USA. e.hesse@uke.de.

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.

PMID:
30902975
PMCID:
PMC6430773
DOI:
10.1038/s41467-019-08778-x
[Indexed for MEDLINE]
Free PMC Article

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