Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss
Abstract Elevated osteoclast (OC) activity is a major contributor to inflammatory bone loss (IBL) during chronic inflammatory diseases. However, the specific OC precursors (OCPs) responding to inflammatory cues and the underlying mechanisms leading to IBL are poorly understood. We identified two dis...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-022-00206-z |
| _version_ | 1811291065910558720 |
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| author | Yaron Meirow Milena Jovanovic Yuval Zur Juliana Habib Daniele Filippo Colombo Nira Twaik Hadas Ashkenazi-Preiser Kerem Ben-Meir Ivan Mikula Or Reuven Guy Kariv Leonor Daniel Saja Baraghithy Yehuda Klein Jeroen Krijgsveld Noam Levaot Michal Baniyash |
| author_facet | Yaron Meirow Milena Jovanovic Yuval Zur Juliana Habib Daniele Filippo Colombo Nira Twaik Hadas Ashkenazi-Preiser Kerem Ben-Meir Ivan Mikula Or Reuven Guy Kariv Leonor Daniel Saja Baraghithy Yehuda Klein Jeroen Krijgsveld Noam Levaot Michal Baniyash |
| author_sort | Yaron Meirow |
| collection | DOAJ |
| description | Abstract Elevated osteoclast (OC) activity is a major contributor to inflammatory bone loss (IBL) during chronic inflammatory diseases. However, the specific OC precursors (OCPs) responding to inflammatory cues and the underlying mechanisms leading to IBL are poorly understood. We identified two distinct OCP subsets: Ly6ChiCD11bhi inflammatory OCPs (iOCPs) induced during chronic inflammation, and homeostatic Ly6ChiCD11blo OCPs (hOCPs) which remained unchanged. Functional and proteomic characterization revealed that while iOCPs were rare and displayed low osteoclastogenic potential under normal conditions, they expanded during chronic inflammation and generated OCs with enhanced activity. In contrast, hOCPs were abundant and manifested high osteoclastogenic potential under normal conditions but generated OCs with low activity and were unresponsive to the inflammatory environment. Osteoclasts derived from iOCPs expressed higher levels of resorptive and metabolic proteins than those generated from hOCPs, highlighting that different osteoclast populations are formed by distinct precursors. We further identified the TNF-α and S100A8/A9 proteins as key regulators that control the iOCP response during chronic inflammation. Furthermore, we demonstrated that the response of iOCPs but not that of hOCPs was abrogated in tnf-α −/− mice, in correlation with attenuated IBL. Our findings suggest a central role for iOCPs in IBL induction. iOCPs can serve as potential biomarkers for IBL detection and possibly as new therapeutic targets to combat IBL in a wide range of inflammatory conditions. |
| first_indexed | 2024-04-13T04:23:47Z |
| format | Article |
| id | doaj.art-244d7c6b4ebd4aa0b1ef0ba3daf0916e |
| institution | Directory Open Access Journal |
| issn | 2095-6231 |
| language | English |
| last_indexed | 2024-04-13T04:23:47Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj.art-244d7c6b4ebd4aa0b1ef0ba3daf0916e2022-12-22T03:02:38ZengNature Publishing GroupBone Research2095-62312022-04-0110111710.1038/s41413-022-00206-zSpecific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone lossYaron Meirow0Milena Jovanovic1Yuval Zur2Juliana Habib3Daniele Filippo Colombo4Nira Twaik5Hadas Ashkenazi-Preiser6Kerem Ben-Meir7Ivan Mikula8Or Reuven9Guy Kariv10Leonor Daniel11Saja Baraghithy12Yehuda Klein13Jeroen Krijgsveld14Noam Levaot15Michal Baniyash16The Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew UniversityDepartment of Physiology and Cell Biology, Ben-Gurion University of the NegevDepartment of Physiology and Cell Biology, Ben-Gurion University of the NegevDepartment of Physiology and Cell Biology, Ben-Gurion University of the NegevDivision of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ)The Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew UniversityThe Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew UniversityThe Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew UniversityThe Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew UniversityThe Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew UniversityThe Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew UniversityThe Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew UniversityInstitute for Drug Research, Faculty of Medicine, The Hebrew UniversityHebrew University-Hadassah School of Dental MedicineDivision of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ)Department of Physiology and Cell Biology, Ben-Gurion University of the NegevThe Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew UniversityAbstract Elevated osteoclast (OC) activity is a major contributor to inflammatory bone loss (IBL) during chronic inflammatory diseases. However, the specific OC precursors (OCPs) responding to inflammatory cues and the underlying mechanisms leading to IBL are poorly understood. We identified two distinct OCP subsets: Ly6ChiCD11bhi inflammatory OCPs (iOCPs) induced during chronic inflammation, and homeostatic Ly6ChiCD11blo OCPs (hOCPs) which remained unchanged. Functional and proteomic characterization revealed that while iOCPs were rare and displayed low osteoclastogenic potential under normal conditions, they expanded during chronic inflammation and generated OCs with enhanced activity. In contrast, hOCPs were abundant and manifested high osteoclastogenic potential under normal conditions but generated OCs with low activity and were unresponsive to the inflammatory environment. Osteoclasts derived from iOCPs expressed higher levels of resorptive and metabolic proteins than those generated from hOCPs, highlighting that different osteoclast populations are formed by distinct precursors. We further identified the TNF-α and S100A8/A9 proteins as key regulators that control the iOCP response during chronic inflammation. Furthermore, we demonstrated that the response of iOCPs but not that of hOCPs was abrogated in tnf-α −/− mice, in correlation with attenuated IBL. Our findings suggest a central role for iOCPs in IBL induction. iOCPs can serve as potential biomarkers for IBL detection and possibly as new therapeutic targets to combat IBL in a wide range of inflammatory conditions.https://doi.org/10.1038/s41413-022-00206-z |
| spellingShingle | Yaron Meirow Milena Jovanovic Yuval Zur Juliana Habib Daniele Filippo Colombo Nira Twaik Hadas Ashkenazi-Preiser Kerem Ben-Meir Ivan Mikula Or Reuven Guy Kariv Leonor Daniel Saja Baraghithy Yehuda Klein Jeroen Krijgsveld Noam Levaot Michal Baniyash Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss Bone Research |
| title | Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss |
| title_full | Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss |
| title_fullStr | Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss |
| title_full_unstemmed | Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss |
| title_short | Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss |
| title_sort | specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss |
| url | https://doi.org/10.1038/s41413-022-00206-z |
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