Lumican promotes joint fibrosis through TGF-β signaling.

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 due to 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 make 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 TLR4 signaling. Previous research has suggested lumican is involved in the pathogenesis of several fibrotic diseases. Since 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 upregulated in the fibrotic joint capsule vs control. We observed lumican significantly enhanced the proliferation, migration and fibroblast-myofibroblast transition of synovial fibroblasts. Moreover, lumican led to increased transcription of α-SMA, MMP-9, Collagen I,PAI-1 and TGF-β in vitro. Lumican treatment promoted collagen lattice contraction in a dose-dependent manner as early as 24 hr after treatment. Thus, our studies reveal that lumican could promote fibroblast-myofibroblast transition and joint contracture.