Fibro-adipogenesis in Injured Rotator Cuff Muscle

Abstract

Purpose of Review Fibro-adipogenic progenitors were first characterized in 2010 and later found to contribute significantly to muscle regeneration and mediate degenerative changes in muscle following injury. These progenitors were also found to have an influence on the rotator cuff muscle’s response to chronic injury which is defined by fibrosis accompanied by massive fatty degeneration. The purpose of this review is to highlight progenitor cells, their contribution to fibro-adipogenesis in rotator cuff tissue, and the factors influencing fibro-adipogenesis in this tissue. Recent Findings Fibro-adipogenic progenitors are a key mediator of the fatty infiltration notably prevalent in rotator cuff injury. Relative to other muscle groups, the rotator cuff has relatively high rates of fibro-adipogenesis following massive chronic rotator cuff tears. This may be linked to the pre-injury density of fibro-adipogenic progenitors in muscle tissue affecting post-injury levels of fibro-adipogenesis. In addition, suprascapular nerve injury in rat models of rotator cuff tears has demonstrated worse, histologic, and biomechanical properties and lower healing rates of rotator cuff repairs. However, fatty infiltration in the rotator cuff following suprascapular nerve compression has been shown to be reversible following release of the nerve compression. Summary The fibro-adipogenic response to acute and chronic injury in rotator cuff tissue is determined by a complex array of factors including progenitor cell influence, transcriptional pathways, chronicity of the injury, anatomic location of injury, microenvironmental influences, and the severity of nerve involvement. Elucidating the complex interactions of these factors will provide potential targets for therapeutic intervention in vivo.

Lineage tracing reveals a novel PDGFRβ+ satellite cell subset that contributes to myo-regeneration of chronically injured rotator cuff muscle

“…Differing from experimental acute injuries that induce sustained muscle regeneration, massive RC tears induced by irreversible RC TTDN result in chronic and severe muscle atrophy, fibrosis and fatty infiltration 24,29 . We applied in the TAM-induced Pdgfrβ-CreER;mTmG mouse strain the TTDN model and confirmed the kinetics and direction of damage spreading at 5-days, 2-and 6-weeks following induction of injury (Fig.…”

Distinct human skeletal muscle-derived CD90 progenitor subsets for myo-fibro-adipogenic disease modeling and treatment in multiplexed conditions

“…The remarkable capacity of skeletal muscle to regenerate following injury can be severely impaired due to massive muscle wasting caused by repetitive trauma, tendon tears, and chronic injury ( Testa et al, 2020 ; Subhash et al, 2022 ). Rotator cuff (RC) disorders are characterized by prolonged damage to shoulder tendons and muscles.…”

“…The pathogenesis of injury-induced RC disease begins with a primary RC tendon tear, followed by a secondary progressive injury that develops in the shoulder muscles attached to the tendon as a consequence of musculotendinous retraction and subsequent forced uncoupling. Pathologic changes progressively develop in chronically damaged muscles and result in muscle scarring and wasting due to myofiber atrophy ( Shah et al, 2017 ; Bogdanov et al, 2021 ; Subhash et al, 2022 ). Notably, one major factor that sets shoulder muscle tear injuries apart from other forms of skeletal muscle injuries is the massive accumulation of fat tissue in the injured RC ( Davies et al, 2015 ).…”