TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone
Year: 2019
Type: article
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.
Source: Nature Communications
Authors: 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
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: U.S. Department of Veterans Affairs, Alexander von Humboldt-Stiftung, European Commission, Helmholtz-Gemeinschaft, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Mereo BioPharma, National Institutes of Health, Universitätsklinikum Hamburg-Eppendorf, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: Glucocorticoid-induced Atrophy in Bone and Muscle, G1269266635, G1367382179, G1554667050, Verbundvorhaben: iBONE, Integrative Biologie osteoanaboler Netzwerke im Epigenom, Hamburg, G2617391633, G2658038073, Molecular Control of Bone Formation, G2984845088, Investigating Ror2-dependent non-canonical Wnt signaling in bone remodeling, G3998565690, G416001494, G4834597330, Differential TGF-Beta Signaling in Bone Microenviroment: Impact on Tumor Growth, MOLECULAR REGULATION OF OSTEOBLAST MOTILITY AND THE BONE-VASCULAR NICHE, G558130469, G7163833320, G8992108187, G9000076565
OpenAlex ID: W2923959257