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...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.展开更多
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)+4 种基金the Natural Science Foundation of Guangdong Province Grant 2017B030301018the Special Support Program for Training High-Level Talents in Guangdong Grant 2019TQ05Y518the Shenzhen Innovation Committee of Science and Technology Grant JCYJ20220530112817040,ZDSYS20220606101604009the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen E010122002supported by the Lombardi and Shinozuka Experimental Pathology Research Endowment Fund,University of Pittsburgh。
文摘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.
