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 S. Mohammad; Theresa A. Guise; Hanna Taipaleenmäki; Eric Hesse

doi:10.1038/s41467-019-08778-x

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 S. Mohammad, Theresa A. Guise, Hanna Taipaleenmäki, Eric Hesse

Orthopedic Surgery

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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 language	English (US)
Article number	1354
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-08778-x
State	Published - Dec 1 2019

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Saito, H., Gasser, A., Bolamperti, S., Maeda, M., Matthies, L., Jähn, K., Long, C. L., Schlüter, H., Kwiatkowski, M., Saini, V., Pajevic, P. D., Bellido, T., van Wijnen, A. J., Mohammad, K. S., Guise, T. A., Taipaleenmäki, H., & Hesse, E. (2019). TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone. Nature communications, 10(1), Article 1354. https://doi.org/10.1038/s41467-019-08778-x

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, KS, Guise, TA, 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

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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.",

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AU - Matthies, Levi

AU - Jähn, Katharina

AU - Long, Courtney L.

AU - Schlüter, Hartmut

AU - Kwiatkowski, Marcel

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AU - Pajevic, Paola Divieti

AU - Bellido, Teresita

AU - van Wijnen, Andre J.

AU - Mohammad, Khalid S.

AU - Guise, Theresa A.

AU - Taipaleenmäki, Hanna

AU - Hesse, Eric

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

Abstract

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