Mice Lacking Wnt9a or Wnt4 Are Prone to Develop Spontaneous Osteoarthritis With Age and Display Alteration in Either the Trabecular or Cortical Bone Compartment
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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DOI：
10.1002/jbmr.4569
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发表时间：
2022-05
影响因子：
6.2
通讯作者：
S. Teufel;L. Wolff;U. König;Akio Kobayashi;R. Behringer;C. Hartmann
中科院分区：
文献类型：
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作者：
S. Teufel;L. Wolff;U. König;Akio Kobayashi;R. Behringer;C. Hartmann
骨关节炎（OA）是一种常见的关节退行性疾病，具有复杂的多因素病因尚未完全了解。在过去的几年里，Wnt信号通路与骨关节炎有关。在最近的一项全基因组关联研究（GWAS）中，1号染色体上与Wnt3a‐Wnt9a基因位点相关的染色体位置被确定为与拇指骨关节炎内表型相关的最重要位点。先前的研究表明，WNT9a参与维持肘关节在胚胎发生过程中的滑膜细胞特性。在这里，我们报道了Wnt9a在表达Prx1 - Cre或Prg4 - CreER的肢体间质细胞中的条件缺失，随着年龄的增长，小鼠容易发生自发的OA样变化。此外，这些小鼠的骨小梁体积也发生了改变。同样，肢体间质Wnt4条件性缺失的小鼠随着年龄的增长也更容易自发地发生类似OA的关节改变。这些小鼠的皮质骨显示出额外的变化。Wnt9a和Wnt4的联合缺失增加了小鼠发生骨关节炎样变化的可能性，并增强了受影响小鼠的疾病严重程度。©2022作者。由Wiley期刊有限责任公司代表美国骨与矿物研究协会（ASBMR）出版的骨与矿物研究杂志。
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).