Cellular, matrix, and mechano-biological differences in load-bearing versus positional tendons throughout development and aging: a narrative review

Choi, Rachel Koeun; Smith, Margaret M.; Clarke, Elizabeth C.; Little, Christopher B.

doi:10.1080/03008207.2018.1504929

Cited by 13 publications

(14 citation statements)

References 63 publications

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“…Nonetheless, potentially important concerns have been raised regarding the physiological and clinical relevance of rodent tail tendons as a model for human disease and repair 77,117,126 . The most cited shortcoming is the fact that human pathologies typically occur in load-bearing tendons while rodent tail tendons are positional tendons.…”

Section: Tendon Fascicles-a Unique Tool To Study the Tendon Stromal Corementioning

confidence: 99%

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: Tendon Fascicles-a Unique Tool To Study the Tendon Stromal Corementioning

confidence: 99%

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

Wunderli

Blache

Snedeker

2020

Connective Tissue Research

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“…In humans, longitudinal tracking of bone marrow lesions by MRI reveals the clinical relationship of subchondral changes to OA progression and knee pain (42). Although similar end-stage OA phenotypes can arise from age, injury, or other causes (58), PLR may play a causal role in some of these pathological mechanisms, but not others.…”

Section: Glucocorticoid-dependent Repression Of Osteocyte Enzyme Exprmentioning

confidence: 99%

Suppressed Osteocyte Perilacunar / Canalicular Remodeling Plays a Causal Role in Osteoarthritis

Mazur

Woo

Yee

et al. 2019

Preprint

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Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function.Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. To determine if PLR suppression plays a causal role in OA, we ablated the PLR enzyme MMP13 in osteocytes, while leaving chondrocytic MMP13 intact. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, this osteocyte-intrinsic PLR defect was sufficient to reduce cartilage proteoglycan content and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, osteocyte PLR is a critical regulator of cartilage homeostasis. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and identify the causal role of suppressed perilacunar/canalicular remodeling in osteoarthritis.Recent reports have reinvigorated interest in the active role of osteocytes in remodeling their surrounding bone matrix -a process called perilacunar/canalicular remodeling (PLR) (7-10). PLR is a dynamic process by which osteocytes secrete matrix metalloproteinases (MMPs) (11-13), cathepsin K (CatK) (8), and other enzymes (14,15) to dynamically resorb and then replace the local bone matrix. PLR maintains bone material properties (11,16,17), systemic mineral homeostasis (8,10), and the canalicular channels that facilitate osteocyte communication, mechanosensation, and nourishment (7,18,19). Several known regulators of bone homeostasis,

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“…The effects of differential loading of tendons on their changing properties across the lifespan are reviewed by Choi et al (10). Understanding of these effects is complicated by the substantial heterogeneity of tendon which the authors explore here by determining if the distinctions between tendons with primarily extensor positional function and those with primarily flexor load-bearing function are valid.…”

Section: Multiscale Molecular Interactions Of Tendonmentioning

confidence: 99%

Multiscale molecular interactions of tendon

Little

2018

Connective Tissue Research

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Cellular, matrix, and mechano-biological differences in load-bearing versus positional tendons throughout development and aging: a narrative review

Cited by 13 publications

References 63 publications

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

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

Suppressed Osteocyte Perilacunar / Canalicular Remodeling Plays a Causal Role in Osteoarthritis

Multiscale molecular interactions of tendon

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