Mice lacking Wnt9a or Wnt4 are prone to develop spontaneous osteoarthritis with age and display alteration in either the trabecular or cortical bone compartment

AbstractOsteoarthritis (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 GWAS study, the chromosomal location on chromosome 1, linked to theWnt3a-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 ofWnt9a 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 ofWnt4 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 ofWnt9a andWnt4 increased the likelihood of the mice developing osteoarthritis-like changes and enhanced disease severity in the affected mice.

Source: Journal of Bone and Mineral Research - May 13, 2022 Category: Orthopaedics Authors: Stefan Teufel, Lena Wolff, Ulrich K önig, Akio Kobayashi, Richard Behringer, Christine Hartmann Tags: Original Article Source Type: research