Sequential Therapy Of Glucocorticoids And Platelet-rich Plasma For Inflammatory Tendinopathy Repair At The Early Stage

Background:Tendinopathy is an important clinical problem with symptoms of pain and dysfunction.Glucocorticoids is widely used in tendinopathy for improving symptoms,but the long-term effects are not satisfactory.Platelet-rich plasma(PRP)is now considered to be a promising therapy promoting tendon repair and regeneration,but it doesn't always work well.We hypothesized that the inflammatory tendinopathy requires a sequential therapy of GCs and PRP as GCs could provide a low-grade inflammation environment to promote the regeneration effects of PRP.In this study,we aim to compare the treatment effect of PRP on tendinopathy with a primary GCIs at early stage or notMethods:Tendon stem/progenitor cells(TSPCs)were acquired through enzyme digestion procedure from tendon tissue of New Zealand rabbits,and PRP were prepared by using density gradient centrifugation.The altered gene expression of TSPCs cultured with PRP was evaluated by RNA-sequencing(RNA-seq).To evaluate the cell viability,senescence,and apoptosis,TSPCs were cultured with 0.1mg/ml triamcinolone acetonide(TA)or/and 10%PRP after residing in IL-1? induced inflammatory environment.An early tendinopathy model established by local collagenase injection into the rabbit Achilles tendon was used to receive isopycnic NS(NS group),TA(TA group),PRP(PRP group),and TA and PRP successively(TA+PRP group)injection treatments respectively.At 8 weeks,the treated tendons were assessed with magnetic resonance imaging(MRI),histology,transmission electron microscopy(TEM),and mechanical testingResults:The gene ontology(GO)enrichment analysis determined that PRP induced an inflammatory response,regulated cell migration,and remodeled extracellular matrix Compared with the sole use of PRP,the successive use of TA and PRP showed no negative effect in cell viability and senescence,and positive effect in cell apoptosis in in vitro experiments.And in vivo experiments showed that TA+PRP group achieved better results than the other groups in tendon regeneration,which were evidenced by less tendon swelling and abnormal MRI signaling,well-organized and large collagenous fibers,less inflammation cells infiltration and vascular invasion,and high strengthConclusion:This study shows that the primary use of glucocorticoids does not leave obvious deleterious side effects on treated tendon but does promote the regeneration effects of PRP on early inflammatory tendinopathy.The "sequential therapy" of glucocorticoids and PRP provide a new promising theory and therapy idea for tendinopathy in clinical practice.