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首页> 中文期刊> 《骨研究（英文版）》 >Chondrogenesis mediates progression of ankylosing spondylitis through heterotopic ossification

Chondrogenesis mediates progression of ankylosing spondylitis through heterotopic ossification

         
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摘要

Ankylosing spondylitis(AS)is chronic inflammatory arthritis with a progressive fusion of axial joints.Anti-inflammatory treatments such as anti-TNF-αantibody therapy suppress inflammation but do not effectively halt the progression of spine fusion in AS patients.Here we report that the autoimmune inflammation of AS generates a microenvironment that promotes chondrogenesis in spine ligaments as the process of spine fusion.Chondrocyte differentiation was observed in the ligaments of patients with earlystage AS,and cartilage formation was followed by calcification.Moreover,a large number of giant osteoclasts were found in the inflammatory environment of ligaments and on bony surfaces of calcified cartilage.Resorption activity by these giant osteoclasts generated marrow with high levels of active TGF-β,which induced new bone formation in the ligaments.Notably,no Osterix+osteoprogenitors were found in osteoclast resorption areas,indicating uncoupled bone resorption and formation.Even at the late and maturation stages,the uncoupled osteoclast resorption in bony interspinous ligament activates TGF-βto induce the progression of ossification in AS patients.Osteoclast resorption of calcified cartilage-initiated ossification in the progression of AS is a similar pathologic process of acquired heterotopic ossification(HO).Our finding of cartilage formation in the ligaments of AS patients revealed that the pathogenesis of spinal fusion is a process of HO and explained why anti-inflammatory treatments do not slow ankylosing once there is new bone formation in spinal soft tissues.Thus,inhibition of HO formation,such as osteoclast activity,cartilage formation,or TGF-βactivity could be a potential therapy for AS.

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  • 来源
    《骨研究（英文版）》 |2021年第2期|166-177|共12页
  • 作者

    Tao Yu; Qimiao Hu; Senbo An; Mei Wan; Shiwu Dong; Jianzhong Xu; Xisheng Weng; Xu Cao; Jianguo Zhang; Wei Zhu; Xiao Wang; Yun Bai; Bin Feng; Qianyu Zhuang; Chang Han; Shengru Wang;

  • 作者单位

    Department of Orthopedic Surgery Johns Hopkins University School of Medicine Baltimore MD 21205 USA;

    Department of Orthopedics Southwest Hospital Third Military Medical University Chongqing 400038 China;

    Department of Orthopedic Surgery Johns Hopkins University School of Medicine Baltimore MD 21205 USA;

    Department of Orthopedic Surgery Johns Hopkins University School of Medicine Baltimore MD 21205 USA;

    Department of Orthopedic Surgery Johns Hopkins University School of Medicine Baltimore MD 21205 USA;

    Department of Orthopedics Southwest Hospital Third Military Medical University Chongqing 400038 China;

    Department of Orthopedics Southwest Hospital Third Military Medical University Chongqing 400038 China;

    Department of Orthopedics Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College 100730 Beijing China;

    State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Science&Peking Union Medical College 100730 Beijing China;

    Department of Orthopedic Surgery Johns Hopkins University School of Medicine Baltimore MD 21205 USA;

    Department of Orthopedics Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College 100730 Beijing China;

    Department of Orthopedics Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College 100730 Beijing China;

    Department of Orthopedic Surgery Johns Hopkins University School of Medicine Baltimore MD 21205 USA;

    Department of Orthopedics Southwest Hospital Third Military Medical University Chongqing 400038 China;

    Department of Orthopedics Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College 100730 Beijing China;

    Department of Orthopedics Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College 100730 Beijing China;

    Department of Orthopedics Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College 100730 Beijing China;

    Department of Orthopedics Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College 100730 Beijing China;

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