Knee arthrofibrosis,characterized by excessive matrix protein production and deposition,substantially impairs basic daily functions,causing considerable distress and financial burden.However,the underlying pathomechan...Knee arthrofibrosis,characterized by excessive matrix protein production and deposition,substantially impairs basic daily functions,causing considerable distress and financial burden.However,the underlying pathomechanisms remain unclear.Here,we characterized the heterogeneous cell populations and cellular pathways by combination of flow cytometry and single-cell RNA-seq analysis of synovial tissues from six patients with or without knee arthrofibrosis.Increased macrophages and fibroblasts were observed with decreased numbers of fibroblast-like synoviocytes,endothelial cells,vascular smooth muscle cells,and T cells in the arthrofibrosis group compared with negative controls.展开更多
Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury,surgery and infection.Excessive extracellular matrix and adhesions contract pouches,bursae and tendons,ca...Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury,surgery and infection.Excessive extracellular matrix and adhesions contract pouches,bursae and tendons,cause pain and prevent a normal range of joint motion,with devastating consequences for patient quality of life.Arthrofibrosis affects people of all ages,with published rates varying.The risk factors and best management strategies are largely unknown due to a poor understanding of the pathology and lack of diagnostic biomarkers.However,current research into the pathogenesis of fibrosis in organs now informs the understanding of arthrofibrosis.The process begins when stress signals stimulate immune cells.The resulting cascade of cytokines and mediators drives fibroblasts to differentiate into myofibroblasts,which secrete fibrillar collagens and transforming growth factor-β(TGF-β).Positive feedback networks then dysregulate processes that normally terminate healing processes.We propose two subtypes of arthrofibrosis occur:active arthrofibrosis and residual arthrofibrosis.In the latter the fibrogenic processes have resolved but the joint remains stiff.The best therapeutic approach for each subtype may differ significantly.Treatment typically involves surgery,however,a pharmacological approach to correct dysregulated cell signalling could be more effective.Recent research shows that myofibroblasts are capable of reversing differentiation,and understanding the mechanisms of pathogenesis and resolution will be essential for the development of cell-based treatments.Therapies with significant promise are currently available,with more in development,including those that inhibit TGF-βsignalling and epigenetic modifications.This review focuses on pathogenesis of sterile arthrofibrosis and therapeutic treatments.展开更多
Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish a...Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.展开更多
基金The Shanghai Science and Technology Committee(22dz1204700)the MOST Key R&D Program of China(2022YFC2304703,2020YFA0907200)+2 种基金Innovative research team of high-level local universities in Shanghai,the National Natural Science Foundation of China(32270202,82272579,82272570,62372286)the Shanghai Talent Development Fund(No.2021057)the Shanghai Jiao Tong University Science and Technology Innovation Special Fund(No.2021JCPT02).
文摘Knee arthrofibrosis,characterized by excessive matrix protein production and deposition,substantially impairs basic daily functions,causing considerable distress and financial burden.However,the underlying pathomechanisms remain unclear.Here,we characterized the heterogeneous cell populations and cellular pathways by combination of flow cytometry and single-cell RNA-seq analysis of synovial tissues from six patients with or without knee arthrofibrosis.Increased macrophages and fibroblasts were observed with decreased numbers of fibroblast-like synoviocytes,endothelial cells,vascular smooth muscle cells,and T cells in the arthrofibrosis group compared with negative controls.
基金partly supported by a research grant from the National Natural Science Funding of China (81802235)Zhejiang Experimental Animal Science and Technology Project of China (2018C37112)+3 种基金Project of Basic Scientific Research Programme in Wenzhou (Y20180033)the support from Australian Health and Medical Research Council (NHMRC Nos.APP1107828,APP1127396,APP1127156,and APP1163933)Arthritis Foundation of Australia (The H J & G J Mckenzie grant)Western Australia Medical & Health Research Infrastructure Fund
文摘Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury,surgery and infection.Excessive extracellular matrix and adhesions contract pouches,bursae and tendons,cause pain and prevent a normal range of joint motion,with devastating consequences for patient quality of life.Arthrofibrosis affects people of all ages,with published rates varying.The risk factors and best management strategies are largely unknown due to a poor understanding of the pathology and lack of diagnostic biomarkers.However,current research into the pathogenesis of fibrosis in organs now informs the understanding of arthrofibrosis.The process begins when stress signals stimulate immune cells.The resulting cascade of cytokines and mediators drives fibroblasts to differentiate into myofibroblasts,which secrete fibrillar collagens and transforming growth factor-β(TGF-β).Positive feedback networks then dysregulate processes that normally terminate healing processes.We propose two subtypes of arthrofibrosis occur:active arthrofibrosis and residual arthrofibrosis.In the latter the fibrogenic processes have resolved but the joint remains stiff.The best therapeutic approach for each subtype may differ significantly.Treatment typically involves surgery,however,a pharmacological approach to correct dysregulated cell signalling could be more effective.Recent research shows that myofibroblasts are capable of reversing differentiation,and understanding the mechanisms of pathogenesis and resolution will be essential for the development of cell-based treatments.Therapies with significant promise are currently available,with more in development,including those that inhibit TGF-βsignalling and epigenetic modifications.This review focuses on pathogenesis of sterile arthrofibrosis and therapeutic treatments.
基金supported in part by the Ruth Jackson Orthopedic Society and the Harris Orthopedic Laboratoryapproved by the Institutional Care and Use Committee of Massachusetts General Hospital(2020N000081)。
文摘Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.
