Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis

• Published in: eLife Vol. 10
• Main Authors: Best, Katherine T, Korcari, Antonion, Mora, Keshia E, Nichols, Anne Ec, Muscat, Samantha N, Knapp, Emma, Buckley, Mark R, Loiselle, Alayna E
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 22-01-2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Ablation; Animals; Basic Helix-Loop-Helix Transcription Factors - deficiency; Basic Helix-Loop-Helix Transcription Factors - genetics; Collagen; Cytoskeleton; Diphtheria; Efficiency; Female; Genotype & phenotype; Gliding; Homeostasis; Localization; Male; Mechanical properties; Mice; Physiological aspects; regeneration; RNA sequencing; Scleraxis; Stem Cells and Regenerative Medicine; tendon; Tendon Injuries - metabolism; Tendons; Tendons - metabolism; Transcription factors; Wound Healing; mouse; stem cells; Scleraxis; tendon; regeneration; regenerative medicine
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.62203

Despite the requirement for
-lineage (Scx
) cells during tendon development, the function of Scx
cells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted Scx
cells (ScxLin
) prior to tendon injury and repair surgery and hypothesized that ScxLin
mice would exhibit functionally deficient healing compared to wild-type littermates. Surprisingly, depletion of Scx
cells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLin
mice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult Scx
cell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.