Amplification of Mitochondrial Activity in the Healing Response Following Rotator Cuff Tendon Injury

Finosh G. Thankam, Isaiah S. Chandra, Anuradha N. Kovilam, Connor G. Diaz, Benjamin T. Volberding, Matthew Dilisio, Mohamed M. Radwan, R. Michael Gross, Devendra K. Agrawal

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Abstract

Mitochondrial function following rotator cuff tendon injury (RCI) influences the tendon healing. We examined the mitochondrial morphology and function under hypoxia in the shoulder tendon tissue from surgically-induced tenotomy-RCI rat model and cultured swine tenocytes. The tendon tissue was collected post-injury on 3–5 (Group-A), 10–12 (Group-B), and 22–24 (Group-C), days and the corresponding contralateral tendons were used as control for each group. There was higher protein expression of citrate synthase (P < 0.0001) [10.22 MFI (mean fluorescent intensity)] and complex-1 (P = 0.0008) (7.86 MFI) in Group-A and Group-B that decreased in Group-C [(P = 0.0201) (5.78 MFI and (P = 0.7915) (2.32 MFI), respectively] compared to control tendons. The ratio of BAX:Bcl2 (Bcl2 associated x protein:B cell lymphoma 2) in RCI tendons increased by 50.5% (Group-A) and 68.4% (Group-B) and decreased by 25.8% (Group-C) compared to normoxic controls. Hypoxia increased β-tubulin expression (P = 0067) and reduced PGC1-α (P = 0412) expression in the isolated swine tenocytes with no effect on the protein expression of Complex-1 (P = 7409) and citrate synthase (P = 0.3290). Also, the hypoxic tenocytes exhibited about 4-fold increase in mitochondrial superoxide (P < 0.0001), altered morphology and mitochondrial pore integrity, and increase in mitochondrial density compared to normoxic controls. These findings suggest the critical role of mitochondria in the RCI healing response.

Original languageEnglish (US)
Article number17027
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • General

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    Thankam, F. G., Chandra, I. S., Kovilam, A. N., Diaz, C. G., Volberding, B. T., Dilisio, M., Radwan, M. M., Gross, R. M., & Agrawal, D. K. (2018). Amplification of Mitochondrial Activity in the Healing Response Following Rotator Cuff Tendon Injury. Scientific Reports, 8(1), [17027]. https://doi.org/10.1038/s41598-018-35391-7