{"title":"ZBTB20调节出生后关节软骨发育和体内平衡:对早发性骨关节炎的影响。","authors":"Xianhua Ma,Fei Jiang,Zhenbang Qin,Yuqing Zhang,Chunchun Wei,Shuang Han,Yuxia Chen,Hai Zhang,Jiang Tao,Zhifang Xie,Weiping J Zhang","doi":"10.1002/art.43393","DOIUrl":null,"url":null,"abstract":"OBJECTIVE\r\nMutations in ZBTB20, a transcription factor, are linked to epiphyseal dysplasia and articular degeneration in humans. This study investigates the role of ZBTB20 in regulating articular cartilage growth and integrity during postnatal development and its implications for early-onset osteoarthritis (OA) in mice.\r\n\r\nMETHODS\r\nWe assessed the spatiotemporal expression of ZBTB20 in articular cartilage using immunostaining and generated an inducible cartilage-specific Zbtb20 knockout mouse model. The impacts of Zbtb20 deletion on cartilage thickness, zonal organization, cellular proliferation, and apoptosis were analyzed. We employed histology, Micro-CT, in situ hybridization, RNA-sequencing, and CUT&Tag to evaluate structural and molecular changes in knees from six to eight male mice per group. ZBTB20 expression in human OA cartilage was analyzed using publicly available datasets.\r\n\r\nRESULTS\r\nZBTB20 was expressed in postnatal developing and adult articular chondrocytes. Postnatal Zbtb20 deletion resulted in progressive thickening of articular cartilage in knees, with a 1.9-fold increase at 2 months of age, particularly in the deep and calcified zones. This was accompanied by chondrocyte overproliferation and differentiation defects, leading to early-onset cartilage degeneration by 6 months. RNA-sequencing and CUT&Tag analyses revealed that ZBTB20 directly regulates a broad set of genes essential for cartilage growth, chondrocyte differentiation, and extracellular matrix organization. Moreover, ZBTB20 expression was significantly reduced in aging-related OA cartilage in both mice and humans, and inducible deletion of Zbtb20 in adult cartilage resulted in severe spontaneous OA-like changes in mice.\r\n\r\nCONCLUSION\r\nZBTB20 is essential for postnatal articular cartilage development and homeostasis, with a protective role in aging-related OA progression.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"52 1","pages":""},"PeriodicalIF":10.9000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ZBTB20 Regulating Postnatal Articular Cartilage Development and Homeostasis: Implications for Early-Onset Osteoarthritis.\",\"authors\":\"Xianhua Ma,Fei Jiang,Zhenbang Qin,Yuqing Zhang,Chunchun Wei,Shuang Han,Yuxia Chen,Hai Zhang,Jiang Tao,Zhifang Xie,Weiping J Zhang\",\"doi\":\"10.1002/art.43393\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"OBJECTIVE\\r\\nMutations in ZBTB20, a transcription factor, are linked to epiphyseal dysplasia and articular degeneration in humans. This study investigates the role of ZBTB20 in regulating articular cartilage growth and integrity during postnatal development and its implications for early-onset osteoarthritis (OA) in mice.\\r\\n\\r\\nMETHODS\\r\\nWe assessed the spatiotemporal expression of ZBTB20 in articular cartilage using immunostaining and generated an inducible cartilage-specific Zbtb20 knockout mouse model. The impacts of Zbtb20 deletion on cartilage thickness, zonal organization, cellular proliferation, and apoptosis were analyzed. We employed histology, Micro-CT, in situ hybridization, RNA-sequencing, and CUT&Tag to evaluate structural and molecular changes in knees from six to eight male mice per group. ZBTB20 expression in human OA cartilage was analyzed using publicly available datasets.\\r\\n\\r\\nRESULTS\\r\\nZBTB20 was expressed in postnatal developing and adult articular chondrocytes. Postnatal Zbtb20 deletion resulted in progressive thickening of articular cartilage in knees, with a 1.9-fold increase at 2 months of age, particularly in the deep and calcified zones. This was accompanied by chondrocyte overproliferation and differentiation defects, leading to early-onset cartilage degeneration by 6 months. RNA-sequencing and CUT&Tag analyses revealed that ZBTB20 directly regulates a broad set of genes essential for cartilage growth, chondrocyte differentiation, and extracellular matrix organization. Moreover, ZBTB20 expression was significantly reduced in aging-related OA cartilage in both mice and humans, and inducible deletion of Zbtb20 in adult cartilage resulted in severe spontaneous OA-like changes in mice.\\r\\n\\r\\nCONCLUSION\\r\\nZBTB20 is essential for postnatal articular cartilage development and homeostasis, with a protective role in aging-related OA progression.\",\"PeriodicalId\":129,\"journal\":{\"name\":\"Arthritis & Rheumatology\",\"volume\":\"52 1\",\"pages\":\"\"},\"PeriodicalIF\":10.9000,\"publicationDate\":\"2025-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Arthritis & Rheumatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/art.43393\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arthritis & Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/art.43393","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
ZBTB20 Regulating Postnatal Articular Cartilage Development and Homeostasis: Implications for Early-Onset Osteoarthritis.
OBJECTIVE
Mutations in ZBTB20, a transcription factor, are linked to epiphyseal dysplasia and articular degeneration in humans. This study investigates the role of ZBTB20 in regulating articular cartilage growth and integrity during postnatal development and its implications for early-onset osteoarthritis (OA) in mice.
METHODS
We assessed the spatiotemporal expression of ZBTB20 in articular cartilage using immunostaining and generated an inducible cartilage-specific Zbtb20 knockout mouse model. The impacts of Zbtb20 deletion on cartilage thickness, zonal organization, cellular proliferation, and apoptosis were analyzed. We employed histology, Micro-CT, in situ hybridization, RNA-sequencing, and CUT&Tag to evaluate structural and molecular changes in knees from six to eight male mice per group. ZBTB20 expression in human OA cartilage was analyzed using publicly available datasets.
RESULTS
ZBTB20 was expressed in postnatal developing and adult articular chondrocytes. Postnatal Zbtb20 deletion resulted in progressive thickening of articular cartilage in knees, with a 1.9-fold increase at 2 months of age, particularly in the deep and calcified zones. This was accompanied by chondrocyte overproliferation and differentiation defects, leading to early-onset cartilage degeneration by 6 months. RNA-sequencing and CUT&Tag analyses revealed that ZBTB20 directly regulates a broad set of genes essential for cartilage growth, chondrocyte differentiation, and extracellular matrix organization. Moreover, ZBTB20 expression was significantly reduced in aging-related OA cartilage in both mice and humans, and inducible deletion of Zbtb20 in adult cartilage resulted in severe spontaneous OA-like changes in mice.
CONCLUSION
ZBTB20 is essential for postnatal articular cartilage development and homeostasis, with a protective role in aging-related OA progression.
期刊介绍:
Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.