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Tendon Extracellular Matrix Assembly, Maintenance and Dysregulation Throughout Life

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Progress in Heritable Soft Connective Tissue Diseases

Abstract

In his Lissner Award medal lecture in 2000, Stephen Cowin asked the question: “How is a tissue built?” It is not a new question, but it remains as relevant today as it did when it was asked 20 years ago. In fact, research on the organization and development of tissue structure has been a primary focus of tendon and ligament research for over two centuries. The tendon extracellular matrix (ECM) is critical to overall tissue function; it gives the tissue its unique mechanical properties, exhibiting complex non-linear responses, viscoelasticity and flow mechanisms, excellent energy storage and fatigue resistance. This matrix also creates a unique microenvironment for resident cells, allowing cells to maintain their phenotype and translate mechanical and chemical signals into biological responses. Importantly, this architecture is constantly remodeled by local cell populations in response to changing biochemical (systemic and local disease or injury) and mechanical (exercise, disuse, and overuse) stimuli. Here, we review the current understanding of matrix remodeling throughout life, focusing on formation and assembly during the postnatal period, maintenance and homeostasis during adulthood, and changes to homeostasis in natural aging. We also discuss advances in model systems and novel tools for studying collagen and non-collagenous matrix remodeling throughout life, and finally conclude by identifying key questions that have yet to be answered.

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Abbreviations

AGEs:

Advanced glycation end-products

Aha:

Azidohomoalanine

BATs:

Bioartificial tendons

CHP:

Collagen hybridizing peptide

CMP:

Collagen mimetic peptide

COMP:

Cartilage oligomeric matrix protein

CSA:

Cross sectional area

DAMPs:

Damage-associated molecular patterns

DIBO:

Dibenzooctyne

DIC:

Differential interference contrast

DTAF:

Dichlorotriazinyl aminofluorescein

ECM:

Extracellular matrix

EDS:

Ehlers-Danlos Syndrome

EM:

Electron microscopy

FACIT:

Fibril-associated collagens with interrupted triple helices

FIC:

Flow-induced crystallization

FN:

Fibronectin

FRET:

Förster resonance energy transfer

GAG:

Glycosaminoglycan

GFP:

Green fluorescent protein

GPC:

Golgi to plasma membrane carrier

IL:

Interleukin

LEs:

Ligament equivalents

Met:

Methionine

MMP:

Matrix metalloproteinase

N3-Pro:

Azido-proline

PGE2:

Prostaglandin E2

ROS:

Reactive oxygen species

SASP:

Senescence-associated secretory phenotype

SHG:

Second harmonic generation

SLRP:

Small leucine rich proteoglycan

TECs:

Tissue engineered constructs

TEM:

Transmission electron microscopy

TSCs:

Tendon stem cells

TSP:

Thrombospondin

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Correspondence to Brianne K. Connizzo .

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Siadat, S.M., Zamboulis, D.E., Thorpe, C.T., Ruberti, J.W., Connizzo, B.K. (2021). Tendon Extracellular Matrix Assembly, Maintenance and Dysregulation Throughout Life. In: Halper, J. (eds) Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology, vol 1348. Springer, Cham. https://doi.org/10.1007/978-3-030-80614-9_3

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