| BackgroundAnterior cruciate ligament injury(ACLI)is a common type of knee injury.It is currently treated clinically with surgery,but it is often associated with secondary osteoarthritis(OA)and the risk of secondary rupture.Non-surgical treatment(conservative treatment)is accompanied by multiple complications and a poor prognosis.In this context,the search for new methods to accelerate ACL healing and remodeling has become a hot research topic in recent years.Pyroptosis,a programmed cell death characterized by the release of inflammatory factors and activation of an intense inflammatory response,is associated with both the inflammatory response and synovial destruction,etc.Ghrelin plays an important role in inhibiting the onset of inflammation,which is an important stage in the process of ACL injury and is a major factor affecting the healing of ACL injuries.However,few studies have explored the role of Ghrelin in the healing of anterior cruciate ligament injuries.ObjectiveTo investigate the correlation between pyroptosis and ACL injury and to verify whether Ghrelin promotes the repair of ACL injury by inhibiting the occurrence of pyroptosis and its possible molecular mechanisms.MethodsIn this study,ACL tissues were collected from clinical patients,ACL fibroblasts(ACLFs)were extracted for subsequent cell experiments,TNF-α(tumor necrosis factor)treats cells in an inflammatory environment that simulates damage,and Ghrelin intervenes in cells in an inflammatory environment.The optimal conditions of TNF-α cells for inflammation model and Ghrelin intervention was determined by CCK-8.The cells were divided into control group;TNF-α inflammation model group;and TNF-α+Ghrelin treatment group.The migratory ability of anterior cruciate ligament fibers and the expression of pyroptosis-related molecules were detected.36 Sprague Dawley rats were divided into three groups,sham group,ACL injury group,and Ghrelin treatment group.The knee joints of rats in each group were injected with saline or Ghrelin for 4w/8w.Histological staining of the knee joints was taken to observe the repair of ACL injury.ResultsHuman anterior cruciate ligament fibroblasts were successfully extracted,and the intervention time of Ghrelin and TNF-α was determined to be 48 h and the intervention concentration was 20 ng/ml.Cell migration was significantly inhibited and the expression of pyroptosis molecules was significantly increased in the TNF-α inflammation model group compared to the control group.Ghrelin intervention improved ACL fibroblast migration and inhibited the expression of pyroptosis molecules.Further studies showed that the expression of the pathway protein NFκB/NLRP3 was significantly increased in the TNF-α inflammation model group,and the expression of the pathway protein NF-κB/NLRP3 was significantly inhibited after Ghrelin intervention.In Sprague Dawley rats with partial ACL injury,Ghrelin treatment for 4 or 8 weeks promoted ACL repair by increasing the number of fibroblasts and optimizing the distribution of collagen fibers compared to the injury group.ConclusionGhrelin may inhibit pyroptosis by inhibiting NF-κB/NLRP3 pathway activity and improve ACL fibroblast migration ability,thus promoting repair of injured ACL,which provides a new strategy for the treatment of ACL injury. |
