Osteomodulin downregulation is associated with osteoarthritis development
Abstract Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA), and osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, spe...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-09-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-023-00286-5 |
| _version_ | 1797577535476727808 |
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| author | Jérémie Zappia Qiao Tong Renée Van der Cruyssen Frederique M. F. Cornelis Cécile Lambert Tiago Pinto Coelho Juliane Grisart Erika Kague Rik J. Lories Marc Muller Dirk Elewaut Chrissy L. Hammond Christelle Sanchez Yves Henrotin |
| author_facet | Jérémie Zappia Qiao Tong Renée Van der Cruyssen Frederique M. F. Cornelis Cécile Lambert Tiago Pinto Coelho Juliane Grisart Erika Kague Rik J. Lories Marc Muller Dirk Elewaut Chrissy L. Hammond Christelle Sanchez Yves Henrotin |
| author_sort | Jérémie Zappia |
| collection | DOAJ |
| description | Abstract Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA), and osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated with bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis, thus controlling the balance of bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA. |
| first_indexed | 2024-03-10T22:09:44Z |
| format | Article |
| id | doaj.art-ce5742b9c2b84d36af2ac8b2853ba263 |
| institution | Directory Open Access Journal |
| issn | 2095-6231 |
| language | English |
| last_indexed | 2024-03-10T22:09:44Z |
| publishDate | 2023-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj.art-ce5742b9c2b84d36af2ac8b2853ba2632023-11-19T12:39:50ZengNature Publishing GroupBone Research2095-62312023-09-0111111610.1038/s41413-023-00286-5Osteomodulin downregulation is associated with osteoarthritis developmentJérémie Zappia0Qiao Tong1Renée Van der Cruyssen2Frederique M. F. Cornelis3Cécile Lambert4Tiago Pinto Coelho5Juliane Grisart6Erika Kague7Rik J. Lories8Marc Muller9Dirk Elewaut10Chrissy L. Hammond11Christelle Sanchez12Yves Henrotin13MusculoSKeletal Innovative Research Lab, Center for Interdisciplinary Research on Medicines, Université de LiègeSchool of Physiology, Pharmacology, and Neuroscience, University of BristolDepartment of Biomedical Molecular Biology, Ghent UniversityLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU LeuvenMusculoSKeletal Innovative Research Lab, Center for Interdisciplinary Research on Medicines, Université de LiègeCardiovascular Sciences, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Université de LiègeArtialis SA, Tour GIGA, CHU Sart-TilmanSchool of Physiology, Pharmacology, and Neuroscience, University of BristolLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU LeuvenLaboratoire d’Organogenèse et Régénération, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Université de LiègeDepartment of Biomedical Molecular Biology, Ghent UniversitySchool of Physiology, Pharmacology, and Neuroscience, University of BristolMusculoSKeletal Innovative Research Lab, Center for Interdisciplinary Research on Medicines, Université de LiègeMusculoSKeletal Innovative Research Lab, Center for Interdisciplinary Research on Medicines, Université de LiègeAbstract Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA), and osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated with bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis, thus controlling the balance of bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.https://doi.org/10.1038/s41413-023-00286-5 |
| spellingShingle | Jérémie Zappia Qiao Tong Renée Van der Cruyssen Frederique M. F. Cornelis Cécile Lambert Tiago Pinto Coelho Juliane Grisart Erika Kague Rik J. Lories Marc Muller Dirk Elewaut Chrissy L. Hammond Christelle Sanchez Yves Henrotin Osteomodulin downregulation is associated with osteoarthritis development Bone Research |
| title | Osteomodulin downregulation is associated with osteoarthritis development |
| title_full | Osteomodulin downregulation is associated with osteoarthritis development |
| title_fullStr | Osteomodulin downregulation is associated with osteoarthritis development |
| title_full_unstemmed | Osteomodulin downregulation is associated with osteoarthritis development |
| title_short | Osteomodulin downregulation is associated with osteoarthritis development |
| title_sort | osteomodulin downregulation is associated with osteoarthritis development |
| url | https://doi.org/10.1038/s41413-023-00286-5 |
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