先天性髋关节发育不良动物模型的制备、评估及遗传学研究进展
Advances in the Preparation, Evaluation, and Genetic Research of Animal Models for Developmental Dysplasia of the Hip
DOI: 10.12677/acm.2025.1541025, PDF,    国家自然科学基金支持
作者: 王贺文*, 王正业*, 刘万林#, 赵振群#：内蒙古医科大学第二附属医院儿童骨科医学中心，内蒙古 呼和浩特
关键词: DDH；动物模型；病理生理机制；模型评估；DDH； Animal Model； Pathophysiological Mechanisms； Model Evaluation
摘要: 本文综述了先天性髋关节发育不良(Developmental Dysplasia of the Hip, DDH)动物模型的制备、评估方法及遗传学研究的最新进展。通过分析手术诱导、自然发生和遗传工程三种模型，深入探讨了DDH的病理生理机制。研究强调了模型评估中整体性能、区分度、校准和重分类能力等关键指标的重要性，并讨论了遗传学研究在识别DDH易感基因和遗传标记方面的成果。本文为DDH的预防、早期诊断和治疗提供了科学基础，并指出了未来研究的方向，有望改善患者预后。
Abstract: This article reviews the latest advancements in the preparation and evaluation methods of animal models for Developmental Dysplasia of the Hip (DDH), as well as progress in genetic research. By analyzing three types of models—surgically induced, naturally occurring, and genetically engineered—the article delves into the pathophysiological mechanisms of DDH. The study emphasizes the importance of key indicators in model evaluation, such as overall performance, discrimination, calibration, and reclassification ability, and discusses the achievements of genetic research in identifying susceptibility genes and genetic markers for DDH. The article provides a scientific basis for the prevention, early diagnosis, and treatment of DDH, and points out the direction for future research, which is expected to improve patient prognosis.
文章引用：王贺文, 王正业, 刘万林, 赵振群. 先天性髋关节发育不良动物模型的制备、评估及遗传学研究进展[J]. 临床医学进展, 2025, 15(4): 1029-1036. https://doi.org/10.12677/acm.2025.1541025

参考文献

[1] 刘万林, 郭文通, 李文琪, 等. 牵引复位有限制动治疗发育性髋关节脱位的远期疗效[J]. 中华小儿外科杂志, 2009, 30(5): 298-301.
[2] 景小博, 张琦豪, 程富礼, 等. 儿童髋关节发育不良相关危险影响因素研究[J]. 中华实验外科杂志, 2021, 38(4): 762-765.
[3] 祁凯, 韦宜山. 发育性髋节发育不良相关基因的系统研究[J]. 临床医学进展, 2024, 14(4): 2891-2897.
[4] 韦宜山, 刘万林, 王国强, 等. 儿童习惯性髋关节脱位病例报告及系统文献复习[J]. 中华骨科杂志, 2022, 42(16): 1065-1076.
[5] Vaquero-Picado, A., González-Morán, G., Garay, E.G. and Moraleda, L. (2019) Developmental Dysplasia of the Hip: Update of Management. EFORT Open Reviews, 4, 548-556. [Google Scholar] [CrossRef] [PubMed]
[6] Pascual‐Garrido, C., Guilak, F., Rai, M.F., Harris, M.D., Lopez, M.J., Todhunter, R.J., et al. (2018) Canine Hip Dysplasia: A Natural Animal Model for Human Developmental Dysplasia of the Hip. Journal of Orthopaedic Research, 36, 1807-1817. [Google Scholar] [CrossRef] [PubMed]
[7] 陈兆强, 杨建平, 张中礼, 等. 婴儿Graf II a型髋关节自然转归及治疗指征的前瞻性研究[J]. 中华骨科杂志, 2017, 37(7): 385-392.
[8] Bakarman, K., Alsiddiky, A.M., Zamzam, M., Alzain, K.O., Alhuzaimi, F.S. and Rafiq, Z. (2023) Developmental Dysplasia of the Hip (DDH): Etiology, Diagnosis, and Management. Cureus, 15, e43207. [Google Scholar] [CrossRef] [PubMed]
[9] Xu, C., Zhang, G., Wang, X., Huang, X., Zhang, J., Han, S., et al. (2024) Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex. Circulation, 149, 1375-1390. [Google Scholar] [CrossRef] [PubMed]
[10] Shamshirgaran, Y., Liu, J., Sumer, H., Verma, P.J. and Taheri-Ghahfarokhi, A. (2022) Tools for Efficient Genome Editing; ZFN, TALEN, and CRISPR. In: Verma, P.J., Sumer, H. and Liu, J., Eds., Applications of Genome Modulation and Editing, Springer, 29-46. [Google Scholar] [CrossRef] [PubMed]
[11] 马宝霞, 沈文璐, 王旭, 等. 基因编辑动物模型在人类疾病研究中的应用[J]. 生物工程学报, 2020, 36(5): 849-860.
[12] Dembic, M., van Brakel Andersen, L., Larsen, M.J., Mechlenburg, I., Søballe, K. and Hertz, J.M. (2022) Whole Exome Sequencing of 28 Families of Danish Descent Reveals Novel Candidate Genes and Pathways in Developmental Dysplasia of the Hip. Molecular Genetics and Genomics, 298, 329-342. [Google Scholar] [CrossRef] [PubMed]
[13] Yang, W., Jin, G., Qian, K., Zhang, C., Zhi, W., Yang, D., et al. (2022) Comprehensive Bioinformatics Analysis of Susceptibility Genes for Developmental Dysplasia of the Hip. Intractable & Rare Diseases Research, 11, 70-80. [Google Scholar] [CrossRef] [PubMed]
[14] Baghdadi, T., Nejadhosseinian, M., Shirkoohi, R., Mostafavi Tabatabaee, R., Tamehri, S.S., Saffari, M., et al. (2019) DNA Hypermethylation of GDF5 in Developmental Dysplasia of the Hip (DDH). Molecular Genetics & Genomic Medicine, 7, e887. [Google Scholar] [CrossRef] [PubMed]
[15] Hatzikotoulas, K., Roposch, A., Shah, K.M., et al. (2018) Genome-Wide Association Study of Developmental Dysplasia of the Hip Identifies an Association with GDF5. Communications Biology, 1, Article No. 56. [Google Scholar] [CrossRef] [PubMed]
[16] Ji, X., Liu, T., Zhao, S., Li, J., Li, L. and Wang, E. (2020) WISP‐2, an Upregulated Gene in Hip Cartilage from the DDH Model Rats, Induces Chondrocyte Apoptosis through PPARγ in vitro. The FASEB Journal, 34, 4904-4917. [Google Scholar] [CrossRef] [PubMed]
[17] Ning, B., Jin, R., Wan, L. and Wang, D. (2018) Cellular and Molecular Changes to Chondrocytes in an in vitro Model of Developmental Dysplasia of the Hip—An Experimental Model of DDH with Swaddling Position. Molecular Medicine Reports, 18, 3873-3881. [Google Scholar] [CrossRef] [PubMed]
[18] Liu, J., Zhou, W., Chen, Y. and Li, L. (2021) Acetabular Development and Fate of Inverted Limbus in Rabbits: Experimental Observation from an Animal Model. Journal of Orthopaedic Research, 39, 2595-2603. [Google Scholar] [CrossRef] [PubMed]
[19] Murakami, T., Ruengsinpinya, L., Takahata, Y., Nakaminami, Y., Hata, K. and Nishimura, R. (2023) HOXA10 Promotes GDF5 Expression in Articular Chondrocytes. Scientific Reports, 13, Article No. 22778. [Google Scholar] [CrossRef] [PubMed]
[20] 崔建洲, 林秀金, 沈汉明. 基因编辑技术(CRISPR-Cas9)在医学领域的应用及其相关伦理问题思考[J]. 中国现代应用药学, 2018, 35(12): 1755-1760.
[21] Ding, Q., Regan, S.N., Xia, Y., Oostrom, L.A., Cowan, C.A. and Musunuru, K. (2013) Enhanced Efficiency of Human Pluripotent Stem Cell Genome Editing through Replacing Talens with CRISPRS. Cell Stem Cell, 12, 393-394. [Google Scholar] [CrossRef] [PubMed]
[22] Van Cleemput, J., Koyuncu, O.O., Laval, K., Engel, E.A. and Enquist, L.W. (2021) CRISPR/Cas9-Constructed Pseudorabies Virus Mutants Reveal the Importance of UL13 in Alphaherpesvirus Escape from Genome Silencing. Journal of Virology, 95. [Google Scholar] [CrossRef] [PubMed]
[23] Schmaranzer, F., Justo, P., Kallini, J.R., Ferrer, M.G., Miller, P., Bixby, S.D., et al. (2023) Hip Morphology on Post-Reduction MRI Predicts Residual Dysplasia 10 Years after Open or Closed Reduction. Journal of Bone and Joint Surgery, 106, 110-119. [Google Scholar] [CrossRef] [PubMed]
[24] Chen, X., Zhang, S., Shi, W., Wu, D., Huang, B., Tao, H., et al. (2023) A Deep Learning Model Adjusting for Infant Gender, Age, Height, and Weight to Determine Whether the Individual Infant Suit Ultrasound Examination of Developmental Dysplasia of the Hip (DDH). Frontiers in Pediatrics, 11, Article 1293320. [Google Scholar] [CrossRef] [PubMed]
[25] Demler, O.V., Pencina, M.J., Cook, N.R. and D’Agostino, R.B. (2017) Asymptotic Distribution of ∆AUC, NRIs, and IDI Based on Theory of U‐Statistics. Statistics in Medicine, 36, 3334-3360. [Google Scholar] [CrossRef] [PubMed]
[26] Vickers, A.J. and Holland, F. (2021) Decision Curve Analysis to Evaluate the Clinical Benefit of Prediction Models. The Spine Journal, 21, 1643-1648. [Google Scholar] [CrossRef] [PubMed]
[27] Collins, G.S., Dhiman, P., Andaur Navarro, C.L., Ma, J., Hooft, L., Reitsma, J.B., et al. (2021) Protocol for Development of a Reporting Guideline (TRIPOD-AI) and Risk of Bias Tool (PROBAST-AI) for Diagnostic and Prognostic Prediction Model Studies Based on Artificial Intelligence. BMJ Open, 11, e048008. [Google Scholar] [CrossRef] [PubMed]
[28] 范建波, 史冬泉, 蒋青. 髋关节发育不良的分子遗传学研究进展[J]. 中华医学遗传学杂志, 2009, 26(6): 674-677.
[29] Kenanidis, E., Gkekas, N.K., Karasmani, A., Anagnostis, P., Christofilopoulos, P. and Tsiridis, E. (2020) Genetic Predisposition to Developmental Dysplasia of the Hip. The Journal of Arthroplasty, 35, 291-300.E1. [Google Scholar] [CrossRef] [PubMed]
[30] 常小丽, 王毅. 发育性髋关节脱位发病相关因素的研究进展[J]. 中华小儿外科杂志, 2016, 37(12): 953-957.
[31] Kiapour, A.M., Cao, J., Young, M. and Capellini, T.D. (2018) The Role of GDF5 Regulatory Regions in Development of Hip Morphology. PLOS ONE, 13, e0202785. [Google Scholar] [CrossRef] [PubMed]
[32] Zhao, X., Liu, S., Yang, Z. and Li, Y. (2024) Molecular Mechanisms and Genetic Factors Contributing to the Developmental Dysplasia of the Hip. Frontiers in Genetics, 15, Article 1413500. [Google Scholar] [CrossRef] [PubMed]

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