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Mice Lacking Wnt9a or Wnt4 Are Prone to Develop Spontaneous Osteoarthritis With Age and Display Alteration in Either the Trabecular or Cortical Bone Compartment |
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| Authors: | Stefan Teufel Lena Wolff Ulrich König Akio Kobayashi Richard Behringer Christine Hartmann |
| Institution: | 1. Institute of Musculoskeletal Medicine, Dept. Bone and Skeletal Research, Medical Faculty of the Westphalian Wilhelms-University, Münster, Germany
Contribution: Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Writing - review & editing;2. Institute of Musculoskeletal Medicine, Dept. Bone and Skeletal Research, Medical Faculty of the Westphalian Wilhelms-University, Münster, Germany Contribution: Investigation, Writing - review & editing;3. Institute of Musculoskeletal Medicine, Dept. Bone and Skeletal Research, Medical Faculty of the Westphalian Wilhelms-University, Münster, Germany Contribution: Resources;4. Institute of Molecular Embryology and Genetics, Department of Kidney Development, Kumamoto University, Japan MD Anderson Cancer Center, Department of Genetics, Division of Basic Sciences, Houston, TX, USA Contribution: Resources;5. MD Anderson Cancer Center, Department of Genetics, Division of Basic Sciences, Houston, TX, USA Contribution: Resources;6. Institute of Musculoskeletal Medicine, Dept. Bone and Skeletal Research, Medical Faculty of the Westphalian Wilhelms-University, Münster, Germany |
| Abstract: | Osteoarthritis (OA) is a common degenerative disease of the joint, with a complex multifactorial not yet fully understood etiology. Over the past years, the Wnt signaling pathway has been implicated in osteoarthritis. In a recent genomewide association study (GWAS), the chromosomal location on chromosome 1, linked to the Wnt3a-Wnt9a gene locus, was identified as the most significant locus associated with a thumb osteoarthritis endophenotype. Previously, it was shown that WNT9a is involved in maintaining synovial cell identity in the elbow joint during embryogenesis. Here, we report that the conditional loss of Wnt9a in the Prx1-Cre expressing limb mesenchyme or Prg4-CreER expressing cells predispositions the mice to develop spontaneous OA-like changes with age. In addition, the trabecular bone volume is altered in these mice. Similarly, mice with a conditional loss of Wnt4 in the limb mesenchyme are also more prone to develop spontaneously OA-like joint alterations with age. These mice display additional alterations in their cortical bone. The combined loss of Wnt9a and Wnt4 increased the likelihood of the mice developing osteoarthritis-like changes and enhanced disease severity in the affected mice. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). |
| Keywords: | Wnt9a Wnt4 RISK FACTOR SPONTANEOUS OSTEOARTHRITIS AGING ΜCT |