Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment
Abstract Intermittent injections of parathyroid hormone (iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone (PTH) primarily results in increased bone resorption. Here, we identified Calca, encoding the sepsis biomarker procal...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-01-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-021-00172-y |
| _version_ | 1819349830144622592 |
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| author | Anke Baranowsky Denise Jahn Shan Jiang Timur Yorgan Peter Ludewig Jessika Appelt Kai K. Albrecht Ellen Otto Paul Knapstein Antonia Donat Jack Winneberger Lana Rosenthal Paul Köhli Cordula Erdmann Melanie Fuchs Karl-Heinz Frosch Serafeim Tsitsilonis Michael Amling Thorsten Schinke Johannes Keller |
| author_facet | Anke Baranowsky Denise Jahn Shan Jiang Timur Yorgan Peter Ludewig Jessika Appelt Kai K. Albrecht Ellen Otto Paul Knapstein Antonia Donat Jack Winneberger Lana Rosenthal Paul Köhli Cordula Erdmann Melanie Fuchs Karl-Heinz Frosch Serafeim Tsitsilonis Michael Amling Thorsten Schinke Johannes Keller |
| author_sort | Anke Baranowsky |
| collection | DOAJ |
| description | Abstract Intermittent injections of parathyroid hormone (iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone (PTH) primarily results in increased bone resorption. Here, we identified Calca, encoding the sepsis biomarker procalcitonin (ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH. |
| first_indexed | 2024-12-24T19:06:45Z |
| format | Article |
| id | doaj.art-ac9d33378f734b29bdcaf0cf65de4ddc |
| institution | Directory Open Access Journal |
| issn | 2095-6231 |
| language | English |
| last_indexed | 2024-12-24T19:06:45Z |
| publishDate | 2022-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj.art-ac9d33378f734b29bdcaf0cf65de4ddc2022-12-21T16:43:05ZengNature Publishing GroupBone Research2095-62312022-01-0110111510.1038/s41413-021-00172-yProcalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatmentAnke Baranowsky0Denise Jahn1Shan Jiang2Timur Yorgan3Peter Ludewig4Jessika Appelt5Kai K. Albrecht6Ellen Otto7Paul Knapstein8Antonia Donat9Jack Winneberger10Lana Rosenthal11Paul Köhli12Cordula Erdmann13Melanie Fuchs14Karl-Heinz Frosch15Serafeim Tsitsilonis16Michael Amling17Thorsten Schinke18Johannes Keller19Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-EppendorfCenter for Musculoskeletal Surgery, Charité-Universitätsmedizin BerlinDepartment of Trauma and Orthopedic Surgery, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfCenter for Musculoskeletal Surgery, Charité-Universitätsmedizin BerlinJulius Wolff Institute for Biomechanics and Musculoskeletal Regeneration, Charité-Universitätsmedizin BerlinCenter for Musculoskeletal Surgery, Charité-Universitätsmedizin BerlinDepartment of Trauma and Orthopedic Surgery, University Medical Center Hamburg-EppendorfDepartment of Trauma and Orthopedic Surgery, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfCenter for Musculoskeletal Surgery, Charité-Universitätsmedizin BerlinDepartment of Trauma and Orthopedic Surgery, University Medical Center Hamburg-EppendorfCenter for Musculoskeletal Surgery, Charité-Universitätsmedizin BerlinDepartment of Trauma and Orthopedic Surgery, University Medical Center Hamburg-EppendorfCenter for Musculoskeletal Surgery, Charité-Universitätsmedizin BerlinDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Trauma and Orthopedic Surgery, University Medical Center Hamburg-EppendorfAbstract Intermittent injections of parathyroid hormone (iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone (PTH) primarily results in increased bone resorption. Here, we identified Calca, encoding the sepsis biomarker procalcitonin (ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.https://doi.org/10.1038/s41413-021-00172-y |
| spellingShingle | Anke Baranowsky Denise Jahn Shan Jiang Timur Yorgan Peter Ludewig Jessika Appelt Kai K. Albrecht Ellen Otto Paul Knapstein Antonia Donat Jack Winneberger Lana Rosenthal Paul Köhli Cordula Erdmann Melanie Fuchs Karl-Heinz Frosch Serafeim Tsitsilonis Michael Amling Thorsten Schinke Johannes Keller Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment Bone Research |
| title | Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment |
| title_full | Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment |
| title_fullStr | Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment |
| title_full_unstemmed | Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment |
| title_short | Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment |
| title_sort | procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent pth treatment |
| url | https://doi.org/10.1038/s41413-021-00172-y |
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