Kobayashi Yasuhiro, Iwamoto Rina, He Zhifeng, Udagawa Nobuyuki
Department of Hard Tissue Research, Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka Gohara, Shiojiri, Nahano, 399-0781, Japan.
Department of Biochemistry, Matsumoto Dental University, 1780 Hirooka Gohara, Shiojiri, Nagano, 399-0781, Japan.
J Bone Miner Metab. 2025 Jan;43(1):39-45. doi: 10.1007/s00774-024-01554-y. Epub 2024 Sep 16.
Wnt signaling plays an important role in the regulation of bone metabolism. Wnt activates the β-catenin-mediated canonical pathway and β-catenin-independent non-canonical pathway. When Wnt ligands bind to the co-receptors low density lipoprotein receptor-related protein (Lrp)5 or Lrp6, and a seven-transmembrane receptor frizzled, the canonical pathway is activated. On the other hand, when Wnt ligands bind to the receptor complex consisting of the co-receptor receptor tyrosine kinase-like orphan receptor (Ror)1 and Ror2 or Ryk and frizzled, the non-canonical pathway is activated. An analysis of loss-of-function and gain-of-function mutations in molecules involved in Wnt signaling (ligands, receptors, and inhibitors) has revealed the mechanisms by which Wnt signaling regulates bone metabolism. In this review, based on transcriptome analyses of Wnt expression in bone tissues including single cell RNA sequence analysis and previous literatures, we herein introduce and discussed the latest findings on the mechanisms by which Wnt ligand mutations impair bone metabolism, especially bone formation.
Wnt信号通路在骨代谢调节中起重要作用。Wnt激活β-连环蛋白介导的经典途径和不依赖β-连环蛋白的非经典途径。当Wnt配体与共受体低密度脂蛋白受体相关蛋白（Lrp）5或Lrp6以及七次跨膜受体卷曲蛋白结合时，经典途径被激活。另一方面，当Wnt配体与由共受体受体酪氨酸激酶样孤儿受体（Ror）1和Ror2或Ryk以及卷曲蛋白组成的受体复合物结合时，非经典途径被激活。对Wnt信号通路相关分子（配体、受体和抑制剂）功能丧失和功能获得突变的分析揭示了Wnt信号通路调节骨代谢的机制。在本综述中，基于对骨组织中Wnt表达的转录组分析，包括单细胞RNA序列分析和以往文献，我们在此介绍并讨论了Wnt配体突变损害骨代谢，尤其是骨形成机制的最新研究结果。
