Abstract
BackgroundIntraarticular scar adhesion refers to a serious complication caused by knee surgery or trauma, leading to various sequelae (e.g., articular cartilage degeneration and knee joint stiffness). Artesunate (ART) has exhibited an effect to suppress fibroblast proliferation, whereas the exact mechanism remains unclear. This study aims to delve into the possible mechanism of ART in suppressing joint adhesion.MethodsThe effect of ART on reduced intraarticular adhesions was ascertained by histological staining and immunohistochemical analysis through vivo experiments. Cell Counting Kit-8 (CCK-8) assay, Western blot analysis, flow cytometry, and tunnel staining were used to detect the effect of ART in promoting fibroblast apoptosis and delve into its possible signaling pathway.ResultsThe results of hematoxylin-eosin (HE) staining suggested that the number of fibroblasts decreased with the increase in ART concentration. The results of Masson staining were similar, with the increase in concentration, the collagen content decreased. Immunohistochemical results showed that the expression of endoplasmic reticulum stress (ERS) characteristic proteins 78 kDa glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) increased in a concentration-dependent manner. CCK-8 results suggested that ART could inhibit fibroblast viability in a concentration- and time-dependent manner. Results of flow cytometry, tunnel staining, and Western blot suggested the apoptosis of fibroblasts occurred after ART treatment. Cells with caspase inhibitors were treated, and apoptotic proteins cleaved-poly ADP-ribose polymerase (cleaved PARP) and cleaved-caspase 3 were detected; the results showed that the apoptotic effect of ART was reduced. The expressions of ERS-related protein CHOP and apoptosis-related protein Bax were upregulated, while the expression of Bcl-2 was downregulated, and the ratio of Bax/Bcl-2 increased in a concentration-dependent manner. Continuous detection of PRKR-like ER kinase (PERK) pathway-related proteins showed that the expression of p-PERK and phosphorylating eukaryotic initiation factor 2α (p-eIF2α) increased in a time-dependent and concentration-dependent manner. PERK pathway inhibitors could partially inhibit ART-mediated apoptosis through PERK pathway.ConclusionsART can promote fibroblast apoptosis through PERK pathway, a classical ERS pathway, and thus prevent fibrosis in the surgical area after joint surgery.
Highlights
The main weight-bearing joint, the knee joint, is prone to injury and degenerative lesions for its high mobility and lack of soft tissue protection
We aimed to investigate whether ART can induce fibroblast apoptosis through PRKR-like endoplasmic reticulum (ER) kinase (PERK) pathway, reduce, or even prevent intraarticular adhesion after knee surgery or trauma
When the cells were grown to nearly 80%, they were rinsed with phosphate buffer saline (PBS) for three times
Summary
The main weight-bearing joint, the knee joint, is prone to injury and degenerative lesions for its high mobility and lack of soft tissue protection. Intraarticular scar adhesion of knee joint refers to a common complication after surgery or trauma, and it critically affects the prognosis of surgery. It has been one of the difficult problems facing the world’s orthopedic department. Some scholars studied the efficacy of manual lysis in the treatment of knee joint adhesions under anesthesia. Their results suggested that this method exhibits significant advantages in the treatment of early knee joint adhesion [2]. Intraarticular scar adhesion refers to a serious complication caused by knee surgery or trauma, leading to various sequelae (e.g., articular cartilage degeneration and knee joint stiffness). This study aims to delve into the possible mechanism of ART in suppressing joint adhesion
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