Disuse Atrophy Accompanied by Intramuscular Ectopic Adipogenesis in Vastus Medialis Muscle of Advanced Osteoarthritis Patients

Abstract

Muscle dysfunction is the most important modifiable mediating factor in primary osteoarthritis (OA) because properly contracting muscles are a key absorber of forces acting on a joint. However, the pathological features of disuse muscle atrophy in OA patients have been rarely studied. Vastus medialis muscles of 14 female patients with OA (age range, 69 to 86 years), largely immobile for 1 or more years, were obtained during arthroplastic surgery and analyzed histologically. These were compared with female patients without arthritis, two with patellar fracture and two with patellar subluxation. Areas occupied by myofibers and adipose tissue were quantified. Large numbers of myofibers were lost in the vastus medialis of OA patients. The loss of myofibers was a possible cause of the reduction in muscle strength of the operated on knee. These changes were significantly correlated with an increase in intramuscular ectopic adipose tissue, and not observed in knees of nonarthritic patients. Resident platelet-derived growth factor receptor α-positive mesenchymal progenitor cells contributed to ectopic adipogenesis in vastus medialis muscles of OA patients. The present study suggests that significant loss of myofibers and ectopic adipogenesis in vastus medialis muscles are common pathological features of advanced knee OA patients with long-term loss of mobility. These changes may be related to the loss of joint function in patients with knee OA.

Evolving Roles of Muscle-Resident Fibro-Adipogenic Progenitors in Health, Regeneration, Neuromuscular Disorders, and Aging

“…These include mouse models of Collagen VI- (Noguchi et al, 2017;Mohassel et al, 2018), human DMD (Uezumi et al, 2014) and mouse models of DMD (Box 1) (Uezumi et al, 2011;Mozzetta et al, 2013;Lemos et al, 2015;Contreras et al, 2016Contreras et al, , 2020Ieronimakis et al, 2016;Kopinke et al, 2017;Mázala et al, 2020;Reggio et al, 2020;Giuliani et al, 2021), Facioscapulohumeral dystrophy (FSHD) (Bosnakovski et al, 2017(Bosnakovski et al, , 2020, Limb-girdle muscular dystrophy (LGMD) (Hogarth et al, 2019), and ALS neuromuscular disease (Gonzalez et al, 2017;Madaro et al, 2018). Increased muscle fibrosis and FAP expansion also occur after single and repeated cycles of intramuscular BaCl 2 , notexin, cardiotoxin, or glycerol administrations (Uezumi et al, 2010;Dadgar et al, 2014;Pessina et al, 2014;Contreras et al, 2016Contreras et al, , 2020Theret et al, 2021), vastus medialis muscles of compromised knee osteoarthritis patients (Ikemoto- Uezumi et al, 2017), human anterior cruciate ligament injuries (Fry et al, 2017), induced hindlimb ischemia (Santini et al, 2020), degenerated muscles of type 2 diabetic patients (Farup et al, 2020), obesity-mediated diaphragm dysfunction of chronic high-fat diet-fed mice (Buras et al, 2019), and surgical muscle traumas including denervation and laceration (Brandan et al, 1992;Pessina et al, 2014;Contreras et al, 2016;Madaro et al, 2018;Rebolledo et al, 2019). Muscle-resident FAP...…”

Evaluation of muscle quality and quantity for the assessment of sarcopenia using mid-thigh computed tomography: a cohort study

“…We consider that the decrease in CTV may be attributable to muscle atrophy and increased fat composition in the muscle. Ikemoto-Uezumi et al [17] compared tissue in the vastus medialis muscle of patients with osteoarthritis and reported that intramuscular adipose tissue (IMAT) and an increased proportion of interstitial tissue were observed. Thus, a decline in CTV with an increased proportion of IMAT was associated with intramuscular fat in ltration [31].…”

“…CT and MRI are considered the gold standards of minimally invasive tests to measure muscle mass [15]; however, their use in the evaluation of muscle quality remains controversial. Goodpaster et al [16] noted a good correlation between CT attenuation value (CTV) and intramuscular fat in ltration, whereas Ikemoto-Uezumi et al [17] reported reduced muscle bers and fatty tissue in ltration in the muscular tissue of the vastus medialis in patients with osteoarthritis. Therefore, it is inferred that CT can evaluate muscle mass and that CTV can evaluate fat in ltration which might be associate with decreased motor function.…”

Assessment of Muscle Quality and Quantity for the Diagnosis of Sarcopenia Using Mid-Thigh Computed Tomography : A Cohort Study

“…Ikemoto-Uezumi et al [17] compared tissue in the vastus medialis muscle of patients with osteoarthritis and reported that intramuscular adipose tissue (IMAT) and an increased proportion of interstitial tissue were observed. Thus, a decline in CTV with an increased proportion of IMAT was associated with intramuscular fat in ltration [27].…”

“…CT and MRI are considered the gold standards of minimally invasive tests to measure muscle mass [15]; however, their use in the evaluation of muscle quality remains controversial. Goodpaster et al [16] noted a good correlation between CT attenuation value (CTV) and intramuscular fat in ltration, whereas Ikemoto-Uezumi et al [17] reported reduced muscle bers and fatty tissue in ltration in the muscular tissue of the vastus medialis in patients with osteoarthritis. Therefore, it is inferred that CT can evaluate muscle mass and that CTV might be able to evaluate motor function, or in other words, muscle quality.…”