HMGB1 mediates the development of tendinopathy due to mechanical overloading

Autoři: Guangyi Zhao aff001;  Jianying Zhang aff001;  Daibang Nie aff001;  Yiqin Zhou aff001;  Feng Li aff001;  Kentaro Onishi aff004;  Timothy Billiar aff005;  James H-C. Wang aff001
Působiště autorů: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America aff001;  Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China aff002;  Joint Surgery and Sports Medicine Department, Shanghai Changzheng Hospital, Second Military Medical University, Huangpu, Shanghai, China aff003;  Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America aff004;  Department of Surgery, University of Pittsburgh, Pennsylvania, United States of America aff005;  Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America aff006
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222369


Mechanical overloading is a major cause of tendinopathy, but the underlying pathogenesis of tendinopathy is unclear. Here we report that high mobility group box1 (HMGB1) is released to the tendon extracellular matrix and initiates an inflammatory cascade in response to mechanical overloading in a mouse model. Moreover, administration of glycyrrhizin (GL), a naturally occurring triterpene and a specific inhibitor of HMGB1, inhibits the tendon’s inflammatory reactions. Also, while prolonged mechanical overloading in the form of long-term intensive treadmill running induces Achilles tendinopathy in mice, administration of GL completely blocks the tendinopathy development. Additionally, mechanical overloading of tendon cells in vitro induces HMGB1 release to the extracellular milieu, thereby eliciting inflammatory and catabolic responses as marked by increased production of prostaglandin E2 (PGE2) and matrix metalloproteinase-3 (MMP-3) in tendon cells. Application of GL abolishes the cellular inflammatory/catabolic responses. Collectively, these findings point to HMGB1 as a key molecule that is responsible for the induction of tendinopathy due to mechanical overloading placed on the tendon.

Klíčová slova:

Cell staining – Collagens – Extracellular matrix – Inflammation – Inflammatory diseases – Nuclear staining – Tendons – Negative staining


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