摘要
Endochondral ossification requires proper control of chondrocyte proliferation,differentiation,survival,and organization.Here we show that knockout ofα-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 thatα-parvin regulates chondrocyte rotation,a process essential for chondrocytes to form columnar structure.Furthermore,loss ofα-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 ofα-parvin in long bone development and shed light on the cellular mechanism through whichα-parvin regulates the longitudinal growth of long bones.
基金
supported by the National Natural Science Foundation of China Grant 82273308,Inno HK@Health,Theme-based Research Scheme (Tl3-602/21-N)
Guangdong-Dongguan Joint Research Scheme Guangdong-Hong Kong-Macao Program (2021B1515130004)
the Natural Science Foundation of Guangdong Province Grant 2017B030301018
the Special Support Program for Training High-Level Talents in Guangdong Grant 2019TQ05Y518
the Shenzhen Innovation Committee of Science and Technology Grant JCYJ20220530112817040,ZDSYS20220606101604009
the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen E010122002
supported by the Lombardi and Shinozuka Experimental Pathology Research Endowment Fund,University of Pittsburgh。