Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation.

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Abstract

[Indexed for MEDLINE] 11. Bone Res. 2023 Aug 22;11(1):46. doi: 10.1038/s41413-023-00284-7. α-parvin controls chondrocyte column formation and regulates long bone development. Yuan J(1)(2), Guo L(3), Wang J(3), Zhou Z(4), Wu C(5)(6). Author information: (1)Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China. (2)School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China. (3)Shenzhen Key Laboratory of Epigenetics and Precision Medicine for Cancers, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China. (4)School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China. zhongjun@hku.hk. (5)Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China. carywu@pitt.edu. (6)Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA. carywu@pitt.edu. Endochondral ossification requires proper control of chondrocyte proliferation, differentiation, survival, and organization. Here we show that knockout of α-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 α-parvin regulates chondrocyte rotation, a process essential for chondrocytes to form columnar structure. Furthermore, loss of α-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 α-parvin in long bone development and shed light on the cellular mechanism through which α-parvin regulates the longitudinal growth of long bones. © 2023. West China School of Stomatology Sichuan University. DOI: 10.1038/s41413-023-00284-7 PMCID: PMC10444880