Tendon response to matrix unloading is determined by the patho-physiological niche

Wunderli, Stefania L.; Blache, Ulrich; Piccoli, Agnese Beretta; Niederöst, Barbara; Holenstein, Claude N.; Passini, Fabian S.; Silván, Unai; Bundgaard, Louise; Keller, Ulrich auf dem; Snedeker, Jess G.

doi:10.1016/j.matbio.2019.12.003

Cited by 47 publications

(49 citation statements)

References 49 publications

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“…However, the response to changes in mechanical loading may be tendon-type specific as shown by comparing mechanically modulated gene expression in Achilles and supraspinatus tendon of rats 112 . Our own studies using mouse tail tendon explants have revealed that this mechanically gated proteolytic response to unloading is strongly dependent on the culture conditions 94,113 , a context-dependency we speculate may be related to relative tissue vascularity. We believe these studies highlight how explant culture systems can be productively and powerfully utilized for investigation of tendon mechanobiology, allowing controlled application (or deprivation) of mechanical loads and the longitudinal functional tracking of mechanical properties.…”

Section: Mechano-culture Systemsmentioning

confidence: 80%

“…However, it is well known that gene expression dramatically changes immediately after extraction and that the process of matrix proteolysis begins. From our own experience, we have learned that factors such as tissue temperature and oxygen tension strongly determine the outcome of explant cultures 113 . By finding an appropriate loading regime and culture conditions that mimic in vivo conditions we may be able to limit such molecular shifts and approach the critical task of better understanding tendon homeostasis 94 .…”

Section: A Perspective On the Utility And Power Of Tail Tendon Explanmentioning

confidence: 99%

“…While existing long-term explant culture studies on tail tendon mostly employ rat tissue, our work on murine tail tendon explants is the first to explore this model 94,113 . This is likely because mouse tendons are relatively small and fragile, which poses challenges in their handling.…”

Section: A Perspective On the Utility And Power Of Tail Tendon Explanmentioning

confidence: 99%

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Tendon explant models for physiologically relevantinvitrostudy of tissue biology – a perspective

Wunderli

Blache

Snedeker

2020

Connective Tissue Research

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Background: Tendon disorders increasingly afflict our aging society but we lack the scientific understanding to clinically address them. Clinically relevant models of tendon disease are urgently needed as established small animal models of tendinopathy fail to capture essential aspects of the disease. Two-dimensional and three-dimensional cell and tissue culture models are similarly limited, lacking many physiological extracellular matrix cues required to maintain tissue homeostasis or guide matrix remodeling. These cues reflect the biochemical and biomechanical status of the tissue, and encode information regarding the mechanical and metabolic competence of the tissue. Tendon explants overcome some of these limitations and have thus emerged as a valuable tool for the discovery and study of mechanisms associated with tendon homeostasis and pathophysiology. Tendon explants retain native cell-cell and cell-matrix connections, while allowing highly reproducible experimental control over extrinsic factors like mechanical loading and nutritional availability. In this sense tendon explant models can deliver insights that are otherwise impossible to obtain from in vivo animal or in vitro cell culture models. Purpose: In this review, we aimed to provide an overview of tissue explant models used in tendon research, with a specific focus on the value of explant culture systems for the controlled study of the tendon core tissue. We discuss their advantages, limitations and potential future utility. We include suggestions and technical recommendations for the successful use of tendon explant cultures and conclude with an outlook on how explant models may be leveraged with state-of-the-art biotechnologies to propel our understanding of tendon physiology and pathology.

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Section: Mechano-culture Systemsmentioning

confidence: 80%

Section: A Perspective On the Utility And Power Of Tail Tendon Explanmentioning

confidence: 99%

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Tendon explant models for physiologically relevantinvitrostudy of tissue biology – a perspective

Wunderli

Blache

Snedeker

2020

Connective Tissue Research

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“…A study released in 2020, dealing with mechanical loading response in hypervascular tendon, demonstrated a rapid cell-mediated tissue breakdown upon mechanical unloading, in contrast to unloaded physiologically normal hypovascular tendon [49]. Analyses of tissue transcriptome and secretome revealed that a stromal niche with elevated tissue oxygenation and temperature drives a ROS-mediated cellular stress response that leads to adoption of an immune-modulatory phenotype within the degrading stromal tissue [49]. Degradomic analysis further showed a surprisingly rich set of active matrix proteases behind the progressive loss of tissue mechanics [49].…”

Section: Tissue Changes: Histopathological Structural Cellular Epimentioning

confidence: 99%

“…Analyses of tissue transcriptome and secretome revealed that a stromal niche with elevated tissue oxygenation and temperature drives a ROS-mediated cellular stress response that leads to adoption of an immune-modulatory phenotype within the degrading stromal tissue [49]. Degradomic analysis further showed a surprisingly rich set of active matrix proteases behind the progressive loss of tissue mechanics [49]. This study is an example of how integrating different large data sets may help us to draw more accurately the interdependent and complex scenario behind tendon pathophysiology.…”

Section: Tissue Changes: Histopathological Structural Cellular Epimentioning

confidence: 99%

Spectrum of Tendon Pathologies: Triggers, Trails and End-State

Steinmann

Pfeifer

Brochhausen

et al. 2020

IJMS

102

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The biggest compartment of the musculoskeletal system is the tendons and ligaments. In particular, tendons are dense tissues connecting muscle to bone that are critical for the integrity, function and locomotion of this system. Due to the increasing age of our society and the overall rise in engagement in extreme and overuse sports, there is a growing prevalence of tendinopathies. Despite the recent advances in tendon research and due to difficult early diagnosis, a multitude of risk factors and vague understanding of the underlying biological mechanisms involved in the progression of tendon injuries, the toolbox of treatment strategies remains limited and non-satisfactory. This review is designed to summarize the current knowledge of triggers, trails and end state of tendinopathies.

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Extrinsic Macrophages Protect While Tendon Progenitors Degrade: Insights from a Tissue Engineered Model of Tendon Compartmental Crosstalk

Stauber

Wolleb

Duss

et al. 2021

Adv Healthcare Materials

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Tendons are among the most mechanically stressed tissues of the body, with a functional core of type-I collagen fibers maintained by embedded stromal fibroblasts known as tenocytes. The intrinsic load-bearing core compartment of tendon is surrounded, nourished, and repaired by the extrinsic peritendon, a synovial-like tissue compartment with access to tendon stem/progenitor cells as well as blood monocytes. In vitro tendon model systems generally lack this important feature of tissue compartmentalization, while in vivo models are cumbersome when isolating multicellular mechanisms. To bridge this gap, an improved in vitro model of explanted tendon core stromal tissue (mouse tail tendon fascicles) surrounded by cell-laden collagen hydrogels that mimic extrinsic tissue compartments is suggested. Using this model, CD146 + tendon stem/progenitor cell and CD45 + F4/80 + bone-marrow derived macrophage activity within a tendon injury-like niche are recapitulated. It is found that extrinsic stromal progenitors recruit to the damaged core, contribute to an overall increase in catabolic ECM gene expression, and accelerate the decrease in mechanical properties. Conversely, it is found that extrinsic bone-marrow derived macrophages in these conditions adopt a proresolution phenotype that mitigates rapid tissue breakdown by outwardly migrated tenocytes and F4/80 + "tenophages" from the intrinsic tissue core.

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Tendon response to matrix unloading is determined by the patho-physiological niche

Cited by 47 publications

References 49 publications

Tendon explant models for physiologically relevantinvitrostudy of tissue biology – a perspective

Tendon explant models for physiologically relevantinvitrostudy of tissue biology – a perspective

Spectrum of Tendon Pathologies: Triggers, Trails and End-State

Extrinsic Macrophages Protect While Tendon Progenitors Degrade: Insights from a Tissue Engineered Model of Tendon Compartmental Crosstalk

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