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Tenascin C Deletion Impairs Tendon Healing and Functional Recovery After Rotator Cuff Repair

ABSTRACT: The biological factors that affect healing after rotator cuff repair (RCR) are not well 63 understood. Genetic variants in the extracellular matrix protein Tenascin C (TNC) are associated 64 with impaired tendon healing and it is expressed in rotator cuff tendon tissue after injury, 65 suggesting it may have a role in the repair process. The purpose of the current study was to 66 determine the role of TNC on tendon healing after RCR in a murine model. The supraspinatus 67 tendon was transected and repaired on the left shoulder of Wild-Type (WT-RCR) and Tenascin 68 C null (Tnc - -RCR) mice. Controls included the unoperated, contralateral shoulder of WT-RCR 69 and Tnc - -RCR mice and unoperated shoulders from WT and Tnc - mice. We performed 70 histologic, activity testing, RNA-seq, and biomechanical analyses. At 8-weeks post-RCR, Tnc71 mice had severe bone and tendon defects following rotator cuff repair. Tnc- -RCR mice had 72 reduced activity after rotator cuff repair including reduced wheel rotations, wheel duration, and 73 wheel episode average velocity compared with WT-RCR. Loss of Tnc following RCR altered 74 gene expression in the shoulder, including upregulation of sex hormone and WNT pathways and 75 a downregulation of inflammation and cell cycle pathways. Tnc - mice had similar biomechanical 76 properties after repair as WT. Further research is required to evaluate tissue specific alterations 77 of Tnc, the interactions of Tnc and sex hormone and inflammation pathways as well as possible 78 adjuvants to improve enthesis healing in the setting of reduced TNC function.

ORGANISM(S): Mus musculus

PROVIDER: GSE271514 | GEO | 2024/09/16

REPOSITORIES: GEO

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Project description:Background Rotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients. Methods RNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT. Results In total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients. Conclusions We preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.

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Tenascin C Deletion Impairs Tendon Healing and Functional Recovery After Rotator Cuff Repair

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