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. van Wijnen, Khalid Mohammad, Theresa Guise, Hanna Taipaleenmäki, Eric Hesse

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1354
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

hormones
Bone Remodeling
Parathyroid Hormone
bones
osteogenesis
Bone
Osteogenesis
osteoblasts
Osteoblasts
osteoporosis
Bone Resorption
Osteoporosis
Semaphorins
Homeodomain Proteins
Anabolic Agents
Bone and Bones
Osteocytes
deletion
secretions
regulators

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone. / Saito, Hiroaki; Gasser, Andreas; Bolamperti, Simona; Maeda, Miki; Matthies, Levi; Jähn, Katharina; Long, Courtney L.; Schlüter, Hartmut; Kwiatkowski, Marcel; Saini, Vaibhav; Pajevic, Paola Divieti; Bellido, Teresita; van Wijnen, Andre J.; Mohammad, Khalid; Guise, Theresa; Taipaleenmäki, Hanna; Hesse, Eric.

In: Nature Communications, Vol. 10, No. 1, 1354, 01.12.2019.

Research output: Contribution to journalArticle

Saito, H, Gasser, A, Bolamperti, S, Maeda, M, Matthies, L, Jähn, K, Long, CL, Schlüter, H, Kwiatkowski, M, Saini, V, Pajevic, PD, Bellido, T, van Wijnen, AJ, Mohammad, K, Guise, T, Taipaleenmäki, H & Hesse, E 2019, 'TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone', Nature Communications, vol. 10, no. 1, 1354. https://doi.org/10.1038/s41467-019-08778-x
Saito, Hiroaki ; Gasser, Andreas ; Bolamperti, Simona ; Maeda, Miki ; Matthies, Levi ; Jähn, Katharina ; Long, Courtney L. ; Schlüter, Hartmut ; Kwiatkowski, Marcel ; Saini, Vaibhav ; Pajevic, Paola Divieti ; Bellido, Teresita ; van Wijnen, Andre J. ; Mohammad, Khalid ; Guise, Theresa ; Taipaleenmäki, Hanna ; Hesse, Eric. / TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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