Cellular response and extracellular matrix breakdown in rotator cuff tendon rupture.
OBJECTIVE
The aim of this study was to investigate the relationship between the disruption of ECM and cellular events including autophagic cell death, apoptosis and cell differentiation into myofibroblasts in the degenerative rotator cuff tendon.


METHODS
Tendon samples were collected from 30 patients undergoing surgery for rotator cuff tears. Apoptosis, autophagic cell death and myofibroblasts of the tendon cells in the ruptured rotator cuff tendon were detected by immunohistochemical staining. The distribution of autophagic cell death, apoptosis, myofibroblasts and cell density were assessed and correlated with the disruption of ECM which was graded 0-3 points using a customized scoring system.


RESULTS
The highest percentage of autophagic cell death (51.9 ± 1.5%) was observed in grade 2 matrix, significantly different from that in matrix graded 0, 1 and 3 (P2Vs0 < 0.001; P2Vs1 < 0.001; P2Vs3 = 0.008, respectively). The highest apoptosis (34.8 ± 1.6%) was found in grade 3 matrix (P3Vs0 < 0.001; P3Vs1 < 0.001; P3Vs2 = 0.044, respectively). The percentage of myofibroblasts significantly increased as the ECM degenerated, with the highest percentage in grade 3 matrix (19.8 ± 1.3%) (P3Vs0 < 0.001; P3Vs11 < 0.001; P3Vs2 = 0.044, respectively). The total cell density varied with the grade of ECM, with maximum cell density in the matrix that was graded 1 (674 ± 27) and minimum cell density in matrix 3 area (395 ± 17) (P1Vs3 < 0.001).


CONCLUSIONS
This study indicates that autophagic cell death, apoptosis and myofibroblast cell differentiation occur in ruptured rotator cuff tissue. These cellular events are closely related to the extent of damage to the ECM structure.
Wu
Bing
B
Centre for Orthopaedic Research, School of Surgery, University of Western Australia, M Block, QE2 Medical Centre, Nedlands, Perth, WA, 6009, Australia.
Chen
Jimin
J
Dela Rosa
Tammyl
T
Yu
Qian
Q
Wang
Allan
A
Xu
Jiake
J
Zheng
Ming-Hao
MH
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D017209:Apoptosis; D001343:Autophagy; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000166:cytology; D017006:Rotator Cuff / Q000473:pathology*; D000070636:Rotator Cuff Injuries; D012421:Rupture