PMID- 31797254
OWN - NLM
STAT- MEDLINE
DCOM- 20200319
LR  - 20210201
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 465
IP  - 1-2
DP  - 2020 Feb
TI  - Matrix regeneration proteins in the hypoxia-triggered exosomes of shoulder 
      tenocytes and adipose-derived mesenchymal stem cells.
PG  - 75-87
LID - 10.1007/s11010-019-03669-7 [doi]
AB  - Regenerative functions of exosomes rely on their contents which are influenced by 
      pathological stimuli, including hypoxia, in rotator cuff tendon injuries (RCTI). 
      The hypoxic environment triggers tenocytes and adjacent adipose-derived 
      mesenchymal stem cells (ADMSCs) to release regenerative mediators to the ECM via 
      the exosomes which elicit autocrine/paracrine responses to protect the tendon 
      matrix from injury. We investigated the exosomal protein contents from tenocytes 
      and subcutaneous ADMSCs from the shoulder of Yucatan microswine cultured under 
      hypoxic conditions (2% O(2)). The exosomal proteins were detected using 
      high-resolution mass spectrometry nano-LC-MS/MS Tribrid system and were compiled 
      using 'Scaffold' software. Hypoxic exosomes from tenocytes and ADMSCs carried 199 
      and 65 proteins, respectively. The key proteins identified by mass spectrometry 
      and associated with ECM homeostasis from hypoxic ADMSCs included MMP2, COL6A, 
      CTSD and TN-C and those from hypoxic tenocytes were THSB1, NSEP1, ITIH4 and TN-C. 
      These findings were confirmed at the mRNA and protein level in the hypoxic ADMSCs 
      and tenocytes. These proteins are involved in multiple signaling pathways of ECM 
      repair/regeneration. This warrants further investigations for their translational 
      significance in the management of RCTI.
FAU - Thankam, Finosh G
AU  - Thankam FG
AD  - Department of Translational Research, Western University of Health Sciences, 309 
      E. Second Street, Pomona, CA, 91766-1854, USA.
FAU - Chandra, Isaiah
AU  - Chandra I
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Diaz, Connor
AU  - Diaz C
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Dilisio, Matthew F
AU  - Dilisio MF
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Fleegel, Jonathan
AU  - Fleegel J
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Gross, R Michael
AU  - Gross RM
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Agrawal, Devendra K
AU  - Agrawal DK
AUID- ORCID: 0000-0001-5445-0013
AD  - Department of Translational Research, Western University of Health Sciences, 309 
      E. Second Street, Pomona, CA, 91766-1854, USA. DAgrawal@WesternU.edu.
LA  - eng
GR  - R01 HL120659/HL/NHLBI NIH HHS/United States
GR  - R01 HL144125/HL/NHLBI NIH HHS/United States
GR  - R01HL120659/NH/NIH HHS/United States
GR  - R01HL144125/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20191203
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Extracellular Matrix Proteins)
SB  - IM
MH  - Adipose Tissue/cytology/*metabolism
MH  - Animals
MH  - Cell Hypoxia
MH  - Exosomes/*metabolism
MH  - Extracellular Matrix Proteins/*metabolism
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Swine
MH  - Swine, Miniature
MH  - Tenocytes/cytology/*metabolism
PMC - PMC6957752
MID - NIHMS1545003
OTO - NOTNLM
OT  - ADMSCs
OT  - Exosomes
OT  - Rotator cuff tendon injury
OT  - Tendon matrix
OT  - Tendon regeneration
OT  - Tenocytes
COIS- Financial and competing interests' disclosure: All authors have read the 
      journal's policy on disclosure of potential conflicts of interest and all authors 
      declare that there is no conflict. No writing assistance was utilized in the 
      production of this manuscript.
EDAT- 2019/12/05 06:00
MHDA- 2020/03/20 06:00
PMCR- 2021/02/01
CRDT- 2019/12/05 06:00
PHST- 2019/09/05 00:00 [received]
PHST- 2019/11/30 00:00 [accepted]
PHST- 2019/12/05 06:00 [pubmed]
PHST- 2020/03/20 06:00 [medline]
PHST- 2019/12/05 06:00 [entrez]
PHST- 2021/02/01 00:00 [pmc-release]
AID - 10.1007/s11010-019-03669-7 [pii]
AID - 10.1007/s11010-019-03669-7 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2020 Feb;465(1-2):75-87. doi: 10.1007/s11010-019-03669-7. Epub 
      2019 Dec 3.