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- Title
Lumican promotes joint fibrosis through TGF‐β signaling.
- Authors
Xiao, Dahai; Liang, Tangzhao; Zhuang, Ze; He, Ronghan; Ren, Jianhua; Jiang, Shihai; Zhu, Lei; Wang, Kun; Shi, Dehai
- Abstract
Joint contracture (also known as arthrofibrosis) is a fibrotic joint disorder characterized by excessive collagen production to form fibrotic scar tissue and adhesions within joint capsules. This can severely affect day‐to‐day activities and quality of life because of a restricted range of motion in affected joints. The precise pathogenic mechanism underlying joint contractures is not fully understood. Lumican belongs to the class II small leucine‐rich repeat proteoglycan superfamily, which makes up collagen fibrils in the extracellular matrix. Lumican is ubiquitously expressed in the skin, liver, heart, uterus and articular cartilage and has reported roles in cell migration, proliferation, angiogenesis and Toll‐like receptor 4 signaling. Previous research has suggested that lumican is involved in the pathogenesis of several fibrotic diseases. Because joint contracture resembles a fibrotic disease, we aimed to investigate the role of lumican in the development of joint contracture in vitro. Here, we showed that protein levels were up‐regulated in the fibrotic joint capsule versus control. We observed that lumican significantly enhanced the proliferation, migration and fibroblast–myofibroblast transition of synovial fibroblasts. Moreover, lumican led to increased transcription of alpha‐smooth muscle actin, matrix metallopeptidase 9, Collagen I, plasminogen activator inhibitor 1 and transforming growth factor‐β in vitro. Lumican treatment promoted collagen lattice contraction in a dose‐dependent manner as early as 24 h after treatment. Thus, our studies reveal that lumican could promote fibroblast–myofibroblast transition and joint contracture.
- Subjects
PLASMINOGEN; PEPTIDASE; PLASMINOGEN activator inhibitors; RANGE of motion of joints; JOINT diseases; ARTICULAR cartilage; TISSUE adhesions
- Publication
FEBS Open Bio, 2020, Vol 10, Issue 11, p2478
- ISSN
2211-5463
- Publication type
Article
- DOI
10.1002/2211-5463.12974