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犬髋关节发育不良:人类发育性髋关节发育不良的天然动物模型。

Canine hip dysplasia: A natural animal model for human developmental dysplasia of the hip.

作者信息

Pascual-Garrido Cecilia, Guilak Farshid, Rai M Farooq, Harris Michael D, Lopez Mandi J, Todhunter Rory J, Clohisy John C

机构信息

Department of Orthopaedic Surgery, School of Medicine, Musculoskeletal Research Center, Washington University, 660 S. Euclid, Campus Box 8233, Saint Louis, Missouri, 63110.

Shriners Hospitals for Children-St. Louis, St. Louis, Missouri.

出版信息

J Orthop Res. 2018 Jul;36(7):1807-1817. doi: 10.1002/jor.23828. Epub 2018 Feb 27.

Abstract

Developmental dysplasia of the hip (DDH) in humans is a common condition that is associated with hip pain, functional limitations, and secondary osteoarthritis (OA). Surgical treatment of DDH has improved in the last decade, allowing excellent outcomes at short- and mid-term follow-up. Still, the etiology, mechanobiology, and pathology underlying this disease are not well understood. A pre-clinical animal model of DDH could help advance the field with a deeper understanding of specific pathways that initiate hip joint degeneration secondary to abnormal biomechanics. An animal model would also facilitate different interventional treatments that could be tested in a rigorous and controlled environment. The dog model exhibits several important characteristics that make it valuable as a pre-clinical animal model for human DDH. Dogs are naturally prone to develop canine hip dysplasia (CHD), which is treated in a similar manner as in humans. Comparable to human DDH, CHD is considered a pre-OA disease; if left untreated it will progress to OA. However, progression to OA is significantly faster in dogs than humans, with progression to OA within 1-2 years of age, associated with their shorter life span compared to humans. Animal studies could potentially reveal the underlying biochemical pathway(s), which can inform refined treatment modalities and provide opportunities for new treatment and prevention targets. Herein, we review the similarities and differences between the two species and outline the argument supporting CHD as an appropriate pre-clinical model of human DDH. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1807-1817, 2018.

摘要

人类髋关节发育不良(DDH)是一种常见病症,与髋关节疼痛、功能受限及继发性骨关节炎(OA)相关。在过去十年中,DDH的外科治疗已有改善,在短期和中期随访中能取得良好疗效。然而,该疾病的病因、力学生物学及病理学仍未得到充分理解。DDH的临床前动物模型有助于深入了解因异常生物力学继发髋关节退变的特定途径,从而推动该领域的发展。动物模型还将促进不同干预治疗方法的开展,这些方法可在严格且可控的环境中进行测试。犬类模型具有几个重要特征,使其成为人类DDH有价值的临床前动物模型。犬类天生易于发生犬髋关节发育不良(CHD),其治疗方式与人类相似。与人类DDH类似,CHD被视为一种骨关节炎前期疾病;若不治疗,将会发展为骨关节炎。然而,犬类发展为骨关节炎的速度比人类快得多,在1 - 2岁时就会发展为骨关节炎,这与其比人类寿命短有关。动物研究可能揭示潜在的生化途径,为优化治疗方式提供依据,并为新的治疗和预防靶点创造机会。在此,我们综述这两个物种之间的异同,并概述支持将CHD作为人类DDH合适临床前模型的依据。© 2017骨科研究协会。由威利期刊公司出版。《矫形外科学研究》36:1807 - 1817,2018年。

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