Early Clinical Observation Of Fatty Infiltration In The Supraspinatus Muscle After Dynamic Superior Capsule Reconstruction And Its Preliminary Mechanism

Massive rotator cuff tear(MRCT)is a severe disease that poses a severe threat to human health,accounting for 10% to 40% of all rotator cuff diseases.MRCT is a tear of more than 5cm or involving two or more tendons in the rotator cuff.Because of its high retear rate postoperative,it not only increases the cost of treatment but also leads to a worse clinical outcome.MRCT is often accompanied by muscle fatty infiltration,which often indicates poor long-term clinical results.When MRCT is fully released arthroscopically while the rotator cuff tendon stump still cannot be fixed in the footprint of the rotator cuff tendon,it is defined as an irreparable massive rotator cuff tear(IMRCT).The unsatisfactory clinical outcome of IMRCT routine surgery is a challenging problem in the field of shoulder surgery.Superior capsule reconstruction(SCR)was first proposed by Professor Teruhisa Mihata of Osaka Medical University in 2012 for IMRCT.The medial end of the autogenous fascia lata is connected to the superior surface of the glenoid and the lateral segment to the footprint of the rotator cuff.It has been clinically confirmed that SCR can effectively restore the static stability of the rotator cuff and significantly improve the clinical outcome.However,SCR does not collect the stump of the supraspinatus tendon,and in most conditions,the fatty infiltration of the supraspinatus muscle was not improved.The previous study showed that the fatty infiltration of skeletal muscle was related to the loss of mechanical stimulation,and the stretching experiment of adipose stem cells also inhibited adipogenic differentiation,which indicates that distraction stress is closely related to fatty infiltration.Based on this,we proposed a dynamic SCR procedure for some IMRCT patients with a 1 cm supraspinatus tendon stump,in which the supraspinatus tendon stump was sutured to the broad fascia to restore the stretching stress of the supraspinatus muscle based on the classical SCR.Theoretically,dynamic SCR has the potential to restore the stretching stress of the supraspinatus tendon,but its improvement and clinical efficacy on the fatty infiltration of the rotator cuff muscle is unclear,and whether dynamic SCR is superior to classical SCR in terms of improving the fatty infiltration of the supraspinatus muscle and clinical outcome has not been reported.Fibro/Adipogenic Progenitor(FAP)is the main source of fatty infiltration in muscle and is a population of multipotent stem cells with the ability to differentiate into fibroblasts and adipocytes.After acute muscle injury,FAPs are activated and proliferated to support muscle injury repair,which leads to fatty infiltration eventually.The results of single-cell sequencing showed that FAPs expressed a large number of Wnt2,Wnt5 a,and Wnt11,and the WNT pathway was involved in the regulation of stretching on the growth,proliferation,and differentiation of many types of stem cells.However,it is not clear whether the recovery of supraspinatus muscle stretching would inhibit the adipogenic differentiation of FAPs and its potential mechanism.Therefore,this study first evaluated the magnetic resonance imaging changes after dynamic SCR for IMRCT,and then compared and analyzed the improvement of muscle fatty infiltration and clinical efficacy of supraspinatus muscle after dynamic SCR and classical SCR.In addition,we also investigated the effects of stretching on the adipogenic differentiation of FAPs and its potential mechanism.MethodsA retrospective analysis was made on all IMRCT patients treated with dynamic SCR and classical SCR with autogenous fascia lata in the Sports Medicine Center of Southwest Hospital from September 2019 to December 2022.Goutallier grades were used to evaluate the fatty infiltration of the supraspinatus muscle.VAS score,the shoulder range of motion,Constant score,and ASES score were used to evaluate shoulder pain,and function respectively,preoperative and at the last follow-up.The flow sorting technique was used to obtain FAPs from the lower limb muscles of the mice.FAPs were divided into a non-stretching group and a stretching group.After stretching FAPs for 24 hours,1Hz,and 8% in vitro,the changes in cytokines,adipogenic markers,and WNT pathway were detected by Western blotting analysis and reverse transcriptase polymerase chain reaction(RT-PCR).ResultsAll 23 patients were followed up for an average of 23.9 months.The fatty infiltration of the supraspinatus muscle in patients with dynamic SCR was significantly improved at the last follow-up(P<0.05).At the same time,the shoulder range of motion,VAS score,Constant score,ASES score,and subacromial space in the last follow-up of dynamic SCR patients were significantly improved as compared with those before the operation(P<0.05).and the improvement of supraspinatus muscle fatty infiltration in patients with dynamic SCR was significantly correlated with the improvement of internal rotation function(P<0.05)At the last follow-up,the degree of fatty infiltration of the supraspinatus muscle in the classical SCR group had no significant change compared with that before the operation,but the range of motion of the shoulder,VAS score,Constant score,ASES score,and subacromial space were significantly improved.Although the improvement of fatty infiltration of the supraspinatus muscle in the dynamic SCR group was significantly better than that in the classical SCR group,there was no significant difference in shoulder range of motion,VAS score,Constant score,ASES score,and subacromial space between the two groups at the last follow-up.Stretching of FAPs increased the release of cytokines related to adipogenic inhibition,including the expression of IL-33,WISP1,IL-6,and Thbs1.Stretching of FAPs also reduced the expression of adipogenic markers,including AP2,PPARγ,and CEBPα.During stretching of FAPs,the expressions of Wnt2 and β-Catenin in FAPs were significantly up-regulated.Conclusion1.Compared to preoperative,dynamic SCR effectively reduced fatty infiltration of the supraspinatus muscle and improved shoulder function,with a significant correlation between the improvement in fatty infiltration and the improvement in shoulder internal rotation function.2.Dynamic SCR was superior to classical SCR in reducing fatty infiltration of the supraspinatus muscle,but there was no difference between the two in shoulder range of motion,pain score,shoulder function score,and subacromial space at the final follow-up,indicating that the early clinical efficacy of dynamic SCR was not inferior to that of classical SCR.3.Adipogenic differentiation of FAPs was significantly inhibited under stretching conditions in vitro and this effect may be mediated by the Wnt2/β-Catenin pathway.