iTRAQ-Based\nProteomic Analysis of Spontaneous Achilles\nTendon Rupture

Spontaneous Achilles tendon rupture (SATR) predominantly\naffects\nmiddle-aged and elderly individuals with chronic injuries. However,\nthe exact cause and mechanism of SATR remain elusive, and potential\ntherapeutic intervention or prevention is still insufficient. The\npresent study aimed to uncover the key pathological molecules by using\niTRAQ proteomics. The results identified 2432 candidate proteins in\nSATR patients using iTRAQ proteomic analysis. A total of 307 differentially\nexpressed proteins (DEPs) were identified and linked to 211 KEGG signaling\npathways including Coronavirus disease (COVID-19), focal adhesion,\nand ribosomes. GO enrichment analysis highlighted significant enrichment\nin processes such as biological adhesion, ossification, lipid (APOA4)\nprocesses, and extracellular matrix (ECM) organization (collagen).\nPPI network analysis identified hub genes such as serum albumin (ALB),\nfibronectin (FN1), and actin cytoplasmic 1. The WB analysis confirmed\nthat FN1 and the receptor for activated C kinase (RACK1) were downregulated\nin the SATR tendon. Immunohistochemical staining revealed that collagen\nI and III were suppressed, while collagen II and APOA4 expression\nwere higher in the SATR pathological tissue (<i>P</i> <\n0.05). However, the primary cultured tenocytes (PCTs) from SATR patients\nshowed enhanced proliferation and, consistent with tissue staining,\nreduced collagen I and III and increased collagen II. Our findings\nreveal vital targets and pathways in SATR’s etiological progression,\noffering a new perspective on the diagnosis, treatment, and prognosis\nof this complex disorder.