TY - JOUR
T1 - Sequential inflammation model for Achilles tendinopathy by elastin degradation with treadmill exercise
AU - Wu, Yi Ting
AU - Wu, Yen Ting
AU - Huang, Tzu Chieh
AU - Su, Fong Chin
AU - Jou, I. Ming
AU - Wu, Chia Ching
N1 - Funding Information:
This study was funded by National Health Research Institutes of Taiwan (grant number NHRI-EX107-10525EI ) and the Ministry of Science and Technology ( MOST 105-2314-B-006-041-MY5 , MOST 104-2320-B-006-003 , MOST 105-2320-B-006-003 , and MOST 106-2320-B-006-003 ).
Funding Information:
This study was supported in part by grants from the Ministry of Science and Technology ( MOST 105-2314-B-006-041-MY5 , MOST 104-2320-B-006-003 , MOST 105-2320-B-006-003 , and MOST 106-2320-B-006-003 to CCW), the National Health Research Institutes of Taiwan ( NHRI-EX106-10525EI to CCW), and the International Center for Wound Repair and Regeneration at National Cheng Kung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, and by the grant of the Ministry of Science and Technology MOST 107-3017-F-006-002 .
Publisher Copyright:
© 2020 The Authors
PY - 2020/7
Y1 - 2020/7
N2 - Background & objective: Tendinopathy is a tendon disease with abnormal mechanical loading to induce chronic repetitive injury. However, lack of a comparable animal model to demonstrate clinical progressions has hindered the understanding of anatomical and pathological changes. The major extracellular matrix (ECM) in the tendon consists of abundant type I collagen (COL) and minimal amount of elastin (ELN). Methods: To study the ECM breakdown and inflammation, rat Achilles tendon was harvested and ex vivo incubated with specific enzymes of elastase (ELNase) or collagenase (COLase). Results: The ELNase broke down ELN, loosened the tendon structure, and increased the COL composition. Increases in cyclooxygenase-2 expression levels in tenocytes were revealed to induce inflammation with either ELNase or COLase. However, incubation of COLase for 12 hours severely digested the tendon. To create a proper ELN degradation in rats, the present study used high-frequency ultrasound to guide the injection of ELNase at the paratendon tissue of the Achilles tendon. The effect of mechanically triggered inflammatory responses was investigated by applying treadmill exercise (15 m/min for 20 min per day). After ELNase injection for 14 and 28 days, a significant loss of ELN was observed, and exercise further facilitated the pathological transition of COL. The dynamics of inflammatory cell recruitments was revealed by specific staining of CD-11b (neutrophils) and CD-68 (macrophage) after in vivo injection of ELNase or COLase for 1, 3, 7, 14, and 28 days. The combination of ELNase and exercise caused early recruitment of neutrophil on day 1 and sequential expression of macrophage on day 7 in peritendinous tissue. Conclusion: These results suggested that ELN degradation with repetitive mechanical loading may present a suitable model for the pathogenesis of tendinopathy. The Translational potential of this article: This discover the role of elastin degradation in tendinopathy and the interaction of exercise in the histological changes. The established the pathological model mimicking the pathogenesis to the human disease by injecting the elastase using ultrasound guidance and then applying treadmill exercise. The loss of elastin and change of collagen composition in clinical tendinopathy samples were observed in the rats. In addition, the sequential inflammation cascades were observed in the histological outcomes with combination of elastase injection and treadmill exercise. Thus, this model may be used to test the clinical treatment of tendinopathy in different stages.
AB - Background & objective: Tendinopathy is a tendon disease with abnormal mechanical loading to induce chronic repetitive injury. However, lack of a comparable animal model to demonstrate clinical progressions has hindered the understanding of anatomical and pathological changes. The major extracellular matrix (ECM) in the tendon consists of abundant type I collagen (COL) and minimal amount of elastin (ELN). Methods: To study the ECM breakdown and inflammation, rat Achilles tendon was harvested and ex vivo incubated with specific enzymes of elastase (ELNase) or collagenase (COLase). Results: The ELNase broke down ELN, loosened the tendon structure, and increased the COL composition. Increases in cyclooxygenase-2 expression levels in tenocytes were revealed to induce inflammation with either ELNase or COLase. However, incubation of COLase for 12 hours severely digested the tendon. To create a proper ELN degradation in rats, the present study used high-frequency ultrasound to guide the injection of ELNase at the paratendon tissue of the Achilles tendon. The effect of mechanically triggered inflammatory responses was investigated by applying treadmill exercise (15 m/min for 20 min per day). After ELNase injection for 14 and 28 days, a significant loss of ELN was observed, and exercise further facilitated the pathological transition of COL. The dynamics of inflammatory cell recruitments was revealed by specific staining of CD-11b (neutrophils) and CD-68 (macrophage) after in vivo injection of ELNase or COLase for 1, 3, 7, 14, and 28 days. The combination of ELNase and exercise caused early recruitment of neutrophil on day 1 and sequential expression of macrophage on day 7 in peritendinous tissue. Conclusion: These results suggested that ELN degradation with repetitive mechanical loading may present a suitable model for the pathogenesis of tendinopathy. The Translational potential of this article: This discover the role of elastin degradation in tendinopathy and the interaction of exercise in the histological changes. The established the pathological model mimicking the pathogenesis to the human disease by injecting the elastase using ultrasound guidance and then applying treadmill exercise. The loss of elastin and change of collagen composition in clinical tendinopathy samples were observed in the rats. In addition, the sequential inflammation cascades were observed in the histological outcomes with combination of elastase injection and treadmill exercise. Thus, this model may be used to test the clinical treatment of tendinopathy in different stages.
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U2 - 10.1016/j.jot.2020.03.004
DO - 10.1016/j.jot.2020.03.004
M3 - Article
AN - SCOPUS:85086770680
SN - 2214-031X
VL - 23
SP - 113
EP - 121
JO - Journal of Orthopaedic Translation
JF - Journal of Orthopaedic Translation
ER -