& alpha;-parvin controls chondrocyte column formation and regulates long bone development

Endochondral ossification requires proper control of chondrocyte proliferation, differentiation, survival, and organization. Here we show that knockout of & alpha;-parvin, an integrin-associated focal adhesion protein, from murine limbs causes defects in endochondral ossification and dwarfism. The mutant long bones were shorter but wider, and the growth plates became disorganized, especially in the proliferative zone. With two-photon time-lapse imaging of bone explant culture, we provide direct evidence showing that & alpha;-parvin regulates chondrocyte rotation, a process essential for chondrocytes to form columnar structure. Furthermore, loss of & alpha;-parvin increased binucleation, elevated cell death, and caused dilation of the resting zones of mature growth plates. Single-cell RNA-seq analyses revealed alterations of transcriptome in all three zones (i.e., resting, proliferative, and hypertrophic zones) of the growth plates. Our results demonstrate a crucial role of & alpha;-parvin in long bone development and shed light on the cellular mechanism through which & alpha;-parvin regulates the longitudinal growth of long bones.

Automated summary

The protein α-Parvin plays a crucial role in bone development. Knocking out α-Parvin leads to defects in endochondral ossification and dwarfism, affecting chondrocyte proliferation, differentiation, survival, and organization. The study demonstrates that α-Parvin regulates chondrocyte rotation, binucleation, cell death, and the structure of growth plates.