Department of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Musculoskeletal Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA.
FASEB J. 2022 Sep;36(9):e22502. doi: 10.1096/fj.202200591R.
Mechanical loading on the skeleton stimulates bone formation. Although the exact mechanism underlying this process remains unknown, a growing body of evidence indicates that the Wnt signaling pathway is necessary for the skeletal response to loading. Recently, we showed that Wnts produced by osteoblast lineage cells mediate the osteo-anabolic response to tibial loading in adult mice. Here, we report that Wnt1 specifically plays a crucial role in mediating the mechano-adaptive response to loading. Independent of loading, short-term loss of Wnt1 in the Osx-lineage resulted in a decreased cortical bone area in the tibias of 5-month-old mice. In females, strain-matched loading enhanced periosteal bone formation in Wnt1F/F controls, but not in Wnt1F/F; OsxCreERT2 knockouts. In males, strain-matched loading increased periosteal bone formation in both control and knockout mice; however, the periosteal relative bone formation rate was 65% lower in Wnt1 knockouts versus controls. Together, these findings show that Wnt1 supports adult bone homeostasis and mediates the bone anabolic response to mechanical loading.
骨骼机械负荷刺激骨形成。尽管这一过程的确切机制尚不清楚，但越来越多的证据表明 Wnt 信号通路对于骨骼对负荷的反应是必要的。最近，我们表明成骨细胞系细胞产生的 Wnts 介导了成年小鼠胫骨负荷的成骨反应。在这里，我们报告 Wnt1 特异性地在介导负荷的机械适应性反应中发挥关键作用。独立于负荷，在 Osx 谱系中短期缺失 Wnt1 会导致 5 月龄小鼠胫骨皮质骨面积减少。在雌性中，应变匹配的加载增强了 Wnt1F/F 对照的骨膜骨形成，但不是 Wnt1F/F；OsxCreERT2 敲除。在雄性中，应变匹配的加载增加了对照和敲除小鼠的骨膜骨形成；然而，骨膜相对骨形成率在 Wnt1 敲除与对照相比低 65%。总之，这些发现表明 Wnt1 支持成人骨稳态，并介导机械负荷对骨合成的反应。
