Kindlin-2 controls TGF-β signalling and Sox9 expression to regulate chondrogenesis

Chuanyue Wu, Hongli Jiao, Yumei Lai, Wei Zheng, Ka Chen, Hong Qu, Weimin Deng, Pingping Song, Ke Zhu, Huiling Cao, Deborah L. Galson, Jie Fan, Hee Jeong Im, Yujie Liu, Ju Chen, Di Chen, Guozhi Xiao

Research output: Contribution to journalArticlepeer-review


The signals that control skeletogenesis are incompletely understood. Here we show that deleting Kindlin-2 in Prx1-expressing mesenchymal progenitors in mice causes neonatal lethality, chondrodysplasia and loss of the skull vault. Kindlin-2 ablation reduces chondrocyte density by decreasing cell proliferation and increasing apoptosis, and disrupts column formation, thus impairing the formation of the primary ossification center and causing severe limb shortening. Remarkably, Kindlin-2 localizes to not only focal adhesions, but also to the nuclei of chondrocytes. Loss of Kindlin-2 reduces, while the overexpression of Kindlin-2 increases, Sox9 expression. Furthermore, the overexpression of Sox9 restores the defects in chondrogenic differentiation induced by Kindlin-2 deletion in vitro. In addition, Kindlin-2 ablation inhibits TGF-β1-induced Smad2 phosphorylation and chondrocyte differentiation. Finally, deleting Kindlin-2 in chondrocytes directly impairs chondrocyte functions, resulting in progressive dwarfism and kyphosis in mice. These studies uncover a previously unrecognized function for Kindlin-2 and a mechanism for regulation of the chondrocyte differentiation programme and chondrogenesis.

Original languageEnglish (US)
Article number7531
JournalNature communications
StatePublished - Jul 7 2015
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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