The ligamentization process of the tendon graft in anterior cruciate ligament(ACL)reconstruction is crucial for graft healing quality,thereby affecting knee joint function.Excessive scar tissue,caused by activation of...The ligamentization process of the tendon graft in anterior cruciate ligament(ACL)reconstruction is crucial for graft healing quality,thereby affecting knee joint function.Excessive scar tissue,caused by activation of trans-differentiation of fibroblasts to myofibroblasts,rather than orientated collagen fibers with normal composition and structure in the graft mid-substance seriously impacts ligamentization.The elucidation of the underlying mechanism behind the graft fibrosis may facilitate modulation of tendon graft ligamentization.Here,we show that transforming growth factor beta 1(TGF-β1)was significantly upregulated with liga-mentization process,contributing to fibroblast to myofibroblast trans-differentiation and thereby leading to impaired collagen orientation with overproduction of collagen type III.Of note,we verified that prostaglandin E2(PGE2),a principal mediator of inflammation secreted by macrophages,significantly reversed TGF-β1-induced trans-differentiation of fibroblasts to myofibroblasts.Importantly,magnesium(Mg)ions were found to upregulate PGE2 production in macrophages,ul-timately favoring inhibition of scar tissue formation and promoting expression of ligament-like phenotype in the graft mid-substance in rats.Consistently,the rats,with injection of the sodium alginate containing Mg ions into knee joint cavity,exhibited significantly improved gait performance and failure load relative to the control group.These results demonstrate the feasibility of using Mg ions to modulate tendon ligamentization in patients after ACL reconstruction.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271381 and 32471378)the Science and Technology Innovation Commission of Shenzhen(Grant No.:JCYJ20220530145601004)+1 种基金Guangdong Basic and Applied Basic Research Foundation(Grant No.:2024A1515010311)Young Elite Sci-entists Sponsorship Program 2023 of ShanDong Provincial Medical As-sociation,and Science and Technology Plan Project of Jinan(202328050).
文摘The ligamentization process of the tendon graft in anterior cruciate ligament(ACL)reconstruction is crucial for graft healing quality,thereby affecting knee joint function.Excessive scar tissue,caused by activation of trans-differentiation of fibroblasts to myofibroblasts,rather than orientated collagen fibers with normal composition and structure in the graft mid-substance seriously impacts ligamentization.The elucidation of the underlying mechanism behind the graft fibrosis may facilitate modulation of tendon graft ligamentization.Here,we show that transforming growth factor beta 1(TGF-β1)was significantly upregulated with liga-mentization process,contributing to fibroblast to myofibroblast trans-differentiation and thereby leading to impaired collagen orientation with overproduction of collagen type III.Of note,we verified that prostaglandin E2(PGE2),a principal mediator of inflammation secreted by macrophages,significantly reversed TGF-β1-induced trans-differentiation of fibroblasts to myofibroblasts.Importantly,magnesium(Mg)ions were found to upregulate PGE2 production in macrophages,ul-timately favoring inhibition of scar tissue formation and promoting expression of ligament-like phenotype in the graft mid-substance in rats.Consistently,the rats,with injection of the sodium alginate containing Mg ions into knee joint cavity,exhibited significantly improved gait performance and failure load relative to the control group.These results demonstrate the feasibility of using Mg ions to modulate tendon ligamentization in patients after ACL reconstruction.
