Cellular and molecular modulation of rotator cuff muscle pathophysiology

Abstract

Rotator cuff (RC) tendon tears are common shoulder injuries that result in irreversible and persistent degeneration of the associated muscles, which is characterized by severe inflammation, atrophy, fibrosis, and fatty infiltration. Although RC muscle degeneration strongly dictates the overall clinical outcomes, strategies to stimulate RC muscle regeneration have largely been overlooked to date. In this review, we highlight the current understanding of the cellular processes that coordinate muscle regeneration, and the roles of muscle resident cells, including immune cells, fibroadipogenic progenitors, and muscle satellite cells in the pathophysiologic regulation of RC muscles following injury. This review also provides perspectives for potential therapies to alleviate the hallmarks of RC muscle degeneration to address current limitations in postsurgical recovery.

WNT7A suppresses adipogenesis of skeletal muscle mesenchymal stem cells and fatty infiltration through the alternative Wnt-Rho-YAP/TAZ signaling axis

“…Persistent fatty infiltration is a chronic hallmark of skeletal muscle injuries and diseases, such as rotator cuff injuries and Duchenne muscular dystrophy ( Fu et al., 2021 ; Li et al., 2015 ). WNT7A has been emerging as a potential therapeutic for muscle diseases and injuries due to its pro-regenerative effects on muscle satellite cells and myofibers ( Han et al., 2019 ; Le Grand et al., 2009 ; von Maltzahn et al., 2011 ), but its effects on FAPs remain unknown.…”

“…Persistent fatty infiltration, known as myosteatosis, is a common hallmark of chronic skeletal muscle injuries and diseases that negatively impacts function and poses significant health and socioeconomic burden ( Minagawa et al., 2013 ; Yamamoto et al., 2010 ). For example, in rotator cuff tendon injuries, irreversible fatty infiltration is prevalent in the associated muscles, which directly increases muscle dysfunction and retear rates following surgical repair ( Fu et al., 2021 ; Gladstone et al., 2007 ; Park et al., 2015b ). In muscular dystrophies, pervasive intramuscular fatty infiltration positively correlates with the disease severity ( Li et al., 2015 ).…”

Wnt7a Suppresses Adipogenesis of Skeletal Muscle Mesenchymal Stem Cells and Fatty Infiltration Through the Alternative Wnt-Rho-YAP/TAZ Signaling Axis

“…Persistent fatty infiltration is a chronic hallmark of skeletal muscle injuries and diseases, such as rotator cuff injuries (Fu et al, 2021). Wnt7a has been emerging as a potential therapeutic for muscle diseases and injuries due to its pro-regenerative effects on muscle satellite cells and myofibers (Han et al, 2019; Le Grand et al, 2009; von Maltzahn et al, 2011), but its effects on FAPs remain unknown.…”

“…Persistent fatty infiltration is a common hallmark of chronic skeletal muscle injuries and diseases that negatively impacts function and poses significant health and socioeconomic burden (Minagawa et al, 2013; Yamamoto et al, 2010). For example, in rotator cuff injuries, irreversible fatty infiltration is prevalent in the associated muscles, which directly increases muscle dysfunction and retear rates following surgical repair (Fu et al, 2021; Gladstone et al, 2007; Park et al, 2015b). In muscular dystrophies, pervasive intramuscular fatty infiltration positively correlates with the disease severity (Li et al, 2015).…”

Regulating Macrophages through Immunomodulatory Biomaterials Is a Promising Strategy for Promoting Tendon-Bone Healing

“…M2 macrophages also produce growth factors, such as TGF-β and VEGF, to regulate tissue regeneration [ 63 , 64 ]. TGF-β is highly attractive to macrophages and can form a positive feedback regulation of TGF-β and other growth factors via stimulating the macrophages [ 65 , 66 ].…”