2. Academic Validation
  3. Downregulation of IL-11 regulates the TGFβ/ERK1/2 signaling pathway to inhibit articular capsule fibrosis and alleviate post-traumatic articular capsule contracture

Downregulation of IL-11 regulates the TGFβ/ERK1/2 signaling pathway to inhibit articular capsule fibrosis and alleviate post-traumatic articular capsule contracture

  • J Shoulder Elbow Surg. 2024 Jul 30:S1058-2746(24)00510-X. doi: 10.1016/j.jse.2024.05.057.
Heng Zheng 1,  Zhen-Jia Zhong 2,  Yi-Chong Wang 3,  Yang-Bai Sun 4,  Feng-Feng Li 5
Affiliations

Affiliations

  • 1 The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
  • 2 The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 3 The 7th People's Hospital of Zhengzhou, Zhengzhou, China.
  • 4 Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: drsunyb@fudan.edu.cn.
  • 5 Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: fengmale@163.com.
PMID: 39089417 DOI: 10.1016/j.jse.2024.05.057
Abstract

Background: Post-traumatic capsular contracture is a common complication of joint injury and surgery. Post-traumatic capsular contracture is associated with fibrosis characterized by excessive differentiation and proliferation of myofibroblasts and abnormal secretion and accumulation of extracellular matrix. Previous studies have suggested that IL11 plays a role in myocardial fibrosis. We thus hypothesized that IL11 may play a fibrotic role during capsular contracture, in order to discover new targets for preventing joint capsule contracture METHODS: We constructed a post-traumatic contracture model by excessively extending the knee joint and fixing the joint in the flexion position, and a post-traumatic joint capsule contracture model was constructed in the wild-type, IL11-/-, IL11R -/-, α-SMA-cre-IL11fl/fl, α-SMA-cre-IL11Rfl/fl mouse strain, with wild-type mice without any treatment of the knee joint as the control group. Fibrotic markers and the expression of IL11 and IL11R in knee joint tissue were detected in each group of mice. The NIH3T3 cell line was used for in vitro analyses. The expression of fibrosis markers, IL11, TGFβ and ERK1/2 were detected by western blot, ELISA and RT-qPCR.

Results: Inhibition of IL11 inhibited ERK1/2 phosphorylation, reduced the secretion of collagen in the joint capsule, and inhibited the excessive differentiation and proliferation of myofibroblasts in the post-traumatic joint capsule contracture, thus alleviating the joint capsule contracture and obtaining better joint mobility.

Conclusion: Downregulation of IL11 in traumatic joint capsule contracture inhibits ERK1/2 phosphorylation, thus significantly relieving joint capsule contracture. Our findings indicate the TGFβ/IL11/ERK1/2 axis is an important pathway for the differentiation of fibroblasts into myofibroblasts. Anti-IL11 treatment is an effective means to prevent traumatic joint capsule contracture.

Keywords

Interleukin 11; collagen; fibrosis; post-traumatic joint capsule contracture; transforming growth factor-β.

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