The Role of SUMO1 Modification of SOX9 in Cartilage Development Stimulated by Zinc Ions in Mice

Zinc ions play a pivotal role in facilitating the development of cartilage in mice. Nevertheless, the precise underlying mechanism remains elusive. Our investigation was centered on elucidating the impact of zinc deficiency on cartilage maturation by modulating SUMO1 and UBC9 at both the protein and...

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Main Authors: Na Xue, Jing Zhao, Jing Yin, Liang Liu, Zhong Yang, Shuchao Zhai, Xiyun Bian, Xiang Gao
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Organogenesis
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Online Access:https://www.tandfonline.com/doi/10.1080/15476278.2025.2460269
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author Na Xue
Jing Zhao
Jing Yin
Liang Liu
Zhong Yang
Shuchao Zhai
Xiyun Bian
Xiang Gao
author_facet Na Xue
Jing Zhao
Jing Yin
Liang Liu
Zhong Yang
Shuchao Zhai
Xiyun Bian
Xiang Gao
author_sort Na Xue
collection DOAJ
description Zinc ions play a pivotal role in facilitating the development of cartilage in mice. Nevertheless, the precise underlying mechanism remains elusive. Our investigation was centered on elucidating the impact of zinc deficiency on cartilage maturation by modulating SUMO1 and UBC9 at both the protein and mRNA levels. We administered a regimen inducing zinc deficiency to gravid mice from E0.5 until euthanasia. Subsequently, we subjected the embryos to scrutiny employing HE, Safranin O staining and IHC. Primary chondrocytes were isolated from fetal mouse femoral condyles and utilized for Western blot analysis to discern the expression profiles of SUMO1, SUMO2/3, UBC9, SOX9, MMP13, Collagen II, RUNX2, and aggrecan. Furthermore, ATDC5 murine chondrocytes were subjected to treatment with ZnCl2, followed by RT-PCR assessment to scrutinize the expression levels of MMP13, Collagen II, RUNX2, and aggrecan. Additionally, we conducted Co-IP assays on ZnCl2-treated ATDC5 cells to explore the interaction between SOX9 and SUMO1. Our investigation unveiled that zinc deficiency led to a reduction in cartilage development, as evidenced by the HE results in fetal murine femur. Moreover, diminished expression levels of SUMO1 and UBC9 were observed in the IHC and Western blot results. Furthermore, Western blot and Co-IP assays revealed an augmented interaction between SOX9 and SUMO1, which was potentiated by ZnCl2 treatment. Significantly, mutations at the SUMOylation site of SOX9 resulted in alterations in the expression patterns of crucial chondrogenesis factors. This research underscores how zinc ions promote cartilage development through the modification of SOX9 by SUMO1.
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spelling doaj-art-0c682b69635a43a188d3d0b66333acf02025-02-05T05:43:40ZengTaylor & Francis GroupOrganogenesis1547-62781555-85922025-12-0121110.1080/15476278.2025.2460269The Role of SUMO1 Modification of SOX9 in Cartilage Development Stimulated by Zinc Ions in MiceNa Xue0Jing Zhao1Jing Yin2Liang Liu3Zhong Yang4Shuchao Zhai5Xiyun Bian6Xiang Gao7Tianjin Key Laboratory of Epigenetics for Organ Development of Preterm Infants, Central Laboratory, Tianjin Fifth Central Hospital, Tianjin, ChinaTianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, ChinaDepartment of Pathology, Tianjin Fifth Central Hospital, Tianjin, ChinaTianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, ChinaDepartment of Orthopedics, Tianjin Fifth Central Hospital, Tianjin, ChinaDepartment of Orthopedics, Tianjin Fifth Central Hospital, Tianjin, ChinaTianjin Key Laboratory of Epigenetics for Organ Development of Preterm Infants, Central Laboratory, Tianjin Fifth Central Hospital, Tianjin, ChinaDepartment of Orthopedics, Tianjin Fifth Central Hospital, Tianjin, ChinaZinc ions play a pivotal role in facilitating the development of cartilage in mice. Nevertheless, the precise underlying mechanism remains elusive. Our investigation was centered on elucidating the impact of zinc deficiency on cartilage maturation by modulating SUMO1 and UBC9 at both the protein and mRNA levels. We administered a regimen inducing zinc deficiency to gravid mice from E0.5 until euthanasia. Subsequently, we subjected the embryos to scrutiny employing HE, Safranin O staining and IHC. Primary chondrocytes were isolated from fetal mouse femoral condyles and utilized for Western blot analysis to discern the expression profiles of SUMO1, SUMO2/3, UBC9, SOX9, MMP13, Collagen II, RUNX2, and aggrecan. Furthermore, ATDC5 murine chondrocytes were subjected to treatment with ZnCl2, followed by RT-PCR assessment to scrutinize the expression levels of MMP13, Collagen II, RUNX2, and aggrecan. Additionally, we conducted Co-IP assays on ZnCl2-treated ATDC5 cells to explore the interaction between SOX9 and SUMO1. Our investigation unveiled that zinc deficiency led to a reduction in cartilage development, as evidenced by the HE results in fetal murine femur. Moreover, diminished expression levels of SUMO1 and UBC9 were observed in the IHC and Western blot results. Furthermore, Western blot and Co-IP assays revealed an augmented interaction between SOX9 and SUMO1, which was potentiated by ZnCl2 treatment. Significantly, mutations at the SUMOylation site of SOX9 resulted in alterations in the expression patterns of crucial chondrogenesis factors. This research underscores how zinc ions promote cartilage development through the modification of SOX9 by SUMO1.https://www.tandfonline.com/doi/10.1080/15476278.2025.2460269ATDC5cartilage developmentSOX9SUMOzinc
spellingShingle Na Xue
Jing Zhao
Jing Yin
Liang Liu
Zhong Yang
Shuchao Zhai
Xiyun Bian
Xiang Gao
The Role of SUMO1 Modification of SOX9 in Cartilage Development Stimulated by Zinc Ions in Mice
Organogenesis
ATDC5
cartilage development
SOX9
SUMO
zinc
title The Role of SUMO1 Modification of SOX9 in Cartilage Development Stimulated by Zinc Ions in Mice
title_full The Role of SUMO1 Modification of SOX9 in Cartilage Development Stimulated by Zinc Ions in Mice
title_fullStr The Role of SUMO1 Modification of SOX9 in Cartilage Development Stimulated by Zinc Ions in Mice
title_full_unstemmed The Role of SUMO1 Modification of SOX9 in Cartilage Development Stimulated by Zinc Ions in Mice
title_short The Role of SUMO1 Modification of SOX9 in Cartilage Development Stimulated by Zinc Ions in Mice
title_sort role of sumo1 modification of sox9 in cartilage development stimulated by zinc ions in mice
topic ATDC5
cartilage development
SOX9
SUMO
zinc
url https://www.tandfonline.com/doi/10.1080/15476278.2025.2460269
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