Chunli Wang1, Qingjia Chi2,3, Yongqiang Sha2, Kang Xu2, Chunming Xu2, Cheng Chen4, Wei Huang4, Peixing Chen2, Peter Chen5, Li Yang6, K L Paul Sung7,8. 1. Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, "111" project Laboratory of Biomechanics and Tissue Repair, Bioengineering College, Chongqing University, Chongqing, 400044, China. lilywang@cqu.edu.cn. 2. Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, "111" project Laboratory of Biomechanics and Tissue Repair, Bioengineering College, Chongqing University, Chongqing, 400044, China. 3. Department of Mechanics and Engineering Structure, Wuhan University of Technology, Wuhan, 430070, China. 4. Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. 5. Departments of Bioengineering and Orthopaedics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0412, USA. 6. Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, "111" project Laboratory of Biomechanics and Tissue Repair, Bioengineering College, Chongqing University, Chongqing, 400044, China. yanglibme@cqu.edu.cn. 7. Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, "111" project Laboratory of Biomechanics and Tissue Repair, Bioengineering College, Chongqing University, Chongqing, 400044, China. klps@cqu.edu.cn. 8. Departments of Bioengineering and Orthopaedics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0412, USA. klps@cqu.edu.cn.
Abstract
OBJECTIVE: Interleukin (IL)-1β in the joint cavity increases to promote healing after anterior cruciate ligament (ACL) injury. Synovial tissue is a major joint microenvironmental regulator after ACL injury. The purpose of this study was to investigate the effects of synovial cells (SCs) on lysyl oxidase (LOX) and matrix metalloproteinase (MMP) production by ACL fibroblasts (ACLfs) in the presence of IL-1β. RESULTS: This study sheds light on the regulation of LOX and MMP-1, -2, -3 expression by ACLfs co-cultured with SCs and treated with IL-1β. LOX and MMP-1, 2, 3 gene/protein expression in IL-1β/stretch-stimulated ACLfs co-cultured with SCs were measured by real-time quantitative PCR and Western blot. Meanwhile, MMP-2 activity was analyzed by zymogram. The results showed that co-culture with SCs increased LOX and MMP-1, -2, -3 gene and protein expression in the presence of IL-1β. Next, ACLfs were subjected to 12% mechanical stretch to simulate pathological injury. Under these conditions, SCs inhibited IL-1β-mediated upregulation of LOXs. However, IL-1β enhanced the expression of MMP-1, -2, -3 in injured ACLfs. CONCLUSIONS: SCs can either inhibit or increase LOX production in the presence of IL-1β, while promoting the accumulation of MMP in injured ACLfs. These results may provide crucial insights into the mechanisms underlying ACL poor healing capacity after injury.
OBJECTIVE: Interleukin (IL)-1β in the joint cavity increases to promote healing after anterior cruciate ligament (ACL) injury. Synovial tissue is a major joint microenvironmental regulator after ACL injury. The purpose of this study was to investigate the effects of synovial cells (SCs) on lysyl oxidase (LOX) and matrix metalloproteinase (MMP) production by ACL fibroblasts (ACLfs) in the presence of IL-1β. RESULTS: This study sheds light on the regulation of LOX and MMP-1, -2, -3 expression by ACLfs co-cultured with SCs and treated with IL-1β. LOX and MMP-1, 2, 3 gene/protein expression in IL-1β/stretch-stimulated ACLfs co-cultured with SCs were measured by real-time quantitative PCR and Western blot. Meanwhile, MMP-2 activity was analyzed by zymogram. The results showed that co-culture with SCs increased LOX and MMP-1, -2, -3 gene and protein expression in the presence of IL-1β. Next, ACLfs were subjected to 12% mechanical stretch to simulate pathological injury. Under these conditions, SCs inhibited IL-1β-mediated upregulation of LOXs. However, IL-1β enhanced the expression of MMP-1, -2, -3 in injured ACLfs. CONCLUSIONS: SCs can either inhibit or increase LOX production in the presence of IL-1β, while promoting the accumulation of MMP in injured ACLfs. These results may provide crucial insights into the mechanisms underlying ACL poor healing capacity after injury.