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 F. Dilisio; Mohamed M. Radwan; R. Michael Gross; Devendra K. Agrawal

doi:10.1038/s41598-018-35391-7

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 F. Dilisio, Mohamed M. Radwan, R. Michael Gross, Devendra K. Agrawal

Department of Surgery

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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 language	English (US)
Article number	17027
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-35391-7
State	Published - Dec 1 2018

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Amplification of Mitochondrial Activity in the Healing Response Following Rotator Cuff Tendon Injury. / Thankam, Finosh G.; Chandra, Isaiah S.; Kovilam, Anuradha N.; Diaz, Connor G.; Volberding, Benjamin T.; Dilisio, Matthew F.; Radwan, Mohamed M.; Gross, R. Michael; Agrawal, Devendra K.

In: Scientific Reports, Vol. 8, No. 1, 17027, 01.12.2018.

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@article{d8165751949a4576a6065b15c64e9441,

title = "Amplification of Mitochondrial Activity in the Healing Response Following Rotator Cuff Tendon Injury",

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.",

author = "Thankam, {Finosh G.} and Chandra, {Isaiah S.} and Kovilam, {Anuradha N.} and Diaz, {Connor G.} and Volberding, {Benjamin T.} and Dilisio, {Matthew F.} and Radwan, {Mohamed M.} and Gross, {R. Michael} and Agrawal, {Devendra K.}",

note = "Funding Information: This work was supported primarily by the State of Nebraska LB506 grant to DKA, and LB692 grant to MFD by Creighton University. The content of this original research article is solely the responsibility of the authors and does not necessarily represent the official views of the State of Nebraska. The authors thank Tom Bargar and Nicholas Conoan of the Electron Microscopy Core Facility (EMCF) at the University of Nebraska Medical Center for technical assistance. The EMCF is supported by state funds from the Nebraska Research Initiative (NRI) and the University of Nebraska Foundation, and institutionally by the Office of the Vice Chancellor for Research. Publisher Copyright: {\textcopyright} 2018, The Author(s).",

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doi = "10.1038/s41598-018-35391-7",

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T1 - Amplification of Mitochondrial Activity in the Healing Response Following Rotator Cuff Tendon Injury

AU - Thankam, Finosh G.

AU - Chandra, Isaiah S.

AU - Kovilam, Anuradha N.

AU - Diaz, Connor G.

AU - Volberding, Benjamin T.

AU - Dilisio, Matthew F.

AU - Radwan, Mohamed M.

AU - Gross, R. Michael

AU - Agrawal, Devendra K.

N1 - Funding Information: This work was supported primarily by the State of Nebraska LB506 grant to DKA, and LB692 grant to MFD by Creighton University. The content of this original research article is solely the responsibility of the authors and does not necessarily represent the official views of the State of Nebraska. The authors thank Tom Bargar and Nicholas Conoan of the Electron Microscopy Core Facility (EMCF) at the University of Nebraska Medical Center for technical assistance. The EMCF is supported by state funds from the Nebraska Research Initiative (NRI) and the University of Nebraska Foundation, and institutionally by the Office of the Vice Chancellor for Research. Publisher Copyright: © 2018, The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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

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