Key result
Hypoxia significantly altered the secretion of extracellular matrix proteins in tenocyte exosomes, reflecting the asymptomatic pathology of rotator cuff tendinopathies.
Why the study?
The pathology of the tendon matrisome in rotator cuff tendinopathies remains asymptomatic, with hypoxia acting as an initiating signal and the secretome of hypoxia-challenged tenocytes reflecting this pathology.
Hypoxia alters the exosomal secretion of extracellular matrix proteins in swine tenocytes, reflecting the asymptomatic molecular pathology of rotator cuff tendinopathies.
Exosomal ECM protein shifts in hypoxic tenocytes reflect asymptomatic RCT pathology; leaves open biomarker or therapeutic potential pending in vivo validation.
The major hallmark of rotator cuff tendinopathies (RCT) is the disorganization of the tendon extracellular matrix (ECM), which is due to a decrease in the ratio of collagen I to collagen III. In addition, the pathology of the tendon matrisome remains asymptomatic, and hypoxia has been identified to be the priming signal to initiate the molecular pathology of RCT. Also, the secretome content of hypoxia-challenged tendon cells (tenocytes) reflects the pathological status of RCT. With this background, the present study was designed to establish the expression status and molecular crosstalk of the ECM component proteins contained in the exosomes of the hypoxia-challenged swine tenocytes. The mass spectrometry analysis revealed the upregulation of COL1A2, P4HA1, PRDX2, P3H1, COL6A1, PPIB, LCN1, and COL3A1 and the downregulation of COLA12, PDIA4, COLG, FN1, CTSK, and TNC in the exosomes of hypoxic tenocytes. These proteins interact with diverse proteins and operate multiple pathways associated with ECM homeostasis and repair as determined by NetworkAnalyst. The functional analysis of these proteins reflects the pathology of tendon ECM, which is correlated with the asymptomatic phase of RCT. Understanding the signaling mediated by these proteins would reveal the underlying molecular pathology and offers translational significance in the diagnosis and management of RCT.
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Thankam et al. (2020) studied Rotator cuff tendinopathies (in vitro model). Hypoxia vs. Normoxia was evaluated on Exosomal protein expression (Relative fold change). Hypoxia significantly altered the secretion of extracellular matrix proteins in tenocyte exosomes, reflecting the asymptomatic pathology of rotator cuff tendinopathies.
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