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Original Article | Open Access

Osteomodulin downregulation is associated with osteoarthritis development

Jérémie Zappia1( )Qiao Tong2Renée Van der Cruyssen3,4Frederique M. F. Cornelis5Cécile Lambert1Tiago Pinto Coelho6,7Juliane Grisart8Erika Kague2Rik J. Lories5,9Marc Muller10Dirk Elewaut3,4Chrissy L. Hammond2Christelle Sanchez1Yves Henrotin1,8,11
MusculoSKeletal Innovative Research Lab, Center for Interdisciplinary Research on Medicines, Université de Liège, Liège, Belgium
School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, UK
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
Cardiovascular Sciences, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Université de Liège, Liège, Belgium
Division of Nephrology, CHU of Liège, Université de Liège, Liège, Belgium
Artialis SA, Tour GIGA, CHU Sart-Tilman, Liège, Belgium
Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium
Laboratoire d’Organogenèse et Régénération, Groupe Interdisciplinaire de Génoprotéomique Appliquée, Université de Liège, Liège, Belgium
Physical Therapy and Rehabilitation Department, Princess Paola Hospital, Vivalia, Marche-en-Famenne, Belgium
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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.

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Bone Research
Article number: 49
Cite this article:
Zappia J, Tong Q, Van der Cruyssen R, et al. Osteomodulin downregulation is associated with osteoarthritis development. Bone Research, 2023, 11: 49. https://doi.org/10.1038/s41413-023-00286-5

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Received: 28 December 2022
Revised: 17 July 2023
Accepted: 12 August 2023
Published: 20 September 2023
© The Author(s) 2023

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