Tendon and multiomics: advantages, advances, and opportunities

Abstract

Tendons heal by fibrosis, which hinders function and increases re-injury risk. Yet the biology that leads to degeneration and regeneration of tendons is not completely understood. Improved understanding of the metabolic nuances that cause diverse outcomes in tendinopathies is required to solve these problems. ‘Omics methods are increasingly used to characterize phenotypes in tissues. Multiomics integrates ‘omic datasets to identify coherent relationships and provide insight into differences in molecular and metabolic pathways between anatomic locations, and disease stages. This work reviews the current literature pertaining to multiomics in tendon and the potential of these platforms to improve tendon regeneration. We assessed the literature and identified areas where ‘omics platforms contribute to the field: (1) Tendon biology where their hierarchical complexity and demographic factors are studied. (2) Tendon degeneration and healing, where comparisons across tendon pathologies are analyzed. (3) The in vitro engineered tendon phenotype, where we compare the engineered phenotype to relevant native tissues. (4) Finally, we review regenerative and therapeutic approaches. We identified gaps in current knowledge and opportunities for future study: (1) The need to increase the diversity of human subjects and cell sources. (2) Opportunities to improve understanding of tendon heterogeneity. (3) The need to use these improvements to inform new engineered and regenerative therapeutic approaches. (4) The need to increase understanding of the development of tendon pathology. Together, the expanding use of various ‘omics platforms and data analysis resulting from these platforms could substantially contribute to major advances in the tendon tissue engineering and regenerative medicine field.

Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment

“…Rotator cuff injuries affect 30% of people over the age of 60, leading to over 600,000 repairs each year in the U.S. (Vitale et al, 2007;Dang and Davies, 2018). Despite their critical musculoskeletal functions, tendons lack the ability to regenerate when injured (Arya and Kulig, 2010;Helland et al, 2013;Derwin and Thomopoulos, 2020;Sarmiento and Little, 2021). Tendons are also commonly associated with heritable connective tissue disorders and birth abnormalities, including Ehlers-Danlos syndrome (EDS) and clubfoot (Browne, 1931;Windisch et al, 2007;Gazit et al, 2016).…”

Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression

“…Metabolomics and proteomics are sensitive trace analysis methods that allow rapid and simultaneous detection of multiple substances by applying small volumes of bodily fluids [7]. They were more commonly used in molecular research and had advantages in analyzing the microenvironment of the organism [8]. It could provide more detailed mechanistic information.…”

Achilles Tendons Display Region-Specific Transcriptomic Signatures Associated With Distinct Mechanical Properties

“…33 An enhanced understanding of regional transcriptional and functional heterogeneity in tendon is important to improve our understanding of the underlying molecular signals that dictate the structure and function of tendon, and this is ultimately necessary to inform targeted use of regenerative medicine and tissue engineering therapies. 37 Therefore, the purpose of this study was to develop a regional transcriptomic atlas of Achilles tendons and evaluate the relationship between region-specific gene expression signatures and mechanical properties in an animal model. We hypothesized that the distal tendon region would have increased stiffness compared with the other 2 regions, with a corresponding increase in the expression of collagen and noncollagen ECM genes.…”