Abstract
Several scientific evidence have shown that exposure to microgravity has a significant impact on the health of the musculoskeletal system by altering the expression of proteins and molecules involved in bone–muscle crosstalk, which is also observed in the research of microgravity effect simulation. Among these, the expression pattern of myostatin appears to play a key role in both load-free muscle damage and the progression of age-related musculoskeletal disorders, such as osteoporosis and sarcopenia. Based on this evidence, we here investigated the efficacy of treatment with anti-myostatin (anti-MSTN) antibodies on primary cultures of human satellite cells exposed to 72 h of random positioning machine (RPM). Cell cultures were obtained from muscle biopsies taken from a total of 30 patients (controls, osteoarthritic, and osteoporotic) during hip arthroplasty. The Pax7 expression by immunofluorescence was carried out for the characterization of satellite cells. We then performed morphological evaluation by light microscopy and immunocytochemical analysis to assess myostatin expression. Our results showed that prolonged RPM exposure not only caused satellite cell death, but also induced changes in myostatin expression levels with group-dependent variations. Surprisingly, we observed that the use of anti-MSTN antibodies induced a significant increase in cell survival after RPM exposure under all experimental conditions. Noteworthy, we found that the negative effect of RPM exposure was counteracted by treatment with anti-MSTN antibodies, which allowed the formation of numerous myotubes. Our results highlight the role of myostatin as a major effector of the cellular degeneration observed with RPM exposure, suggesting it as a potential therapeutic target to slow the muscle mass loss that occurs in the absence of loading.
Highlights
Sarcopenia is a typical pathological condition of aging characterized by a progressive reduction in muscle strength and function leading to physical frailty and an increased risk of falls and fractures (Cariati et al, 2021)
We previously showed by Transmission Electron Microscopy (TEM) analysis the presence of evident signs of cell degeneration in myotubes observed in primary cultures subjected to random positioning machine (RPM) exposure (Tarantino et al, 2020)
The results presented here support the hypothesis of myostatinmediated muscle damage induced by RPM exposure
Summary
Sarcopenia is a typical pathological condition of aging characterized by a progressive reduction in muscle strength and function leading to physical frailty and an increased risk of falls and fractures (Cariati et al, 2021). Several scientific evidence have reported that muscle mass and strength may decrease in response to microgravity and groundbased simulation conditions, resulting in muscle atrophy, changes in muscle fiber composition and gene expression, as well as a reduction in regenerative muscle growth (Fitts et al, 2010; Narici and de Boer, 2011; Tanaka et al, 2017) These changes are generally associated with bone mass loss, alterations in the balance between osteoblasts and osteoclasts activities, as well as increased bone resorption and inhibition of new bone formation by osteoblasts (Arfat et al, 2014; Grimm et al, 2016). We observed increased BMP-2 expression levels in all experimental groups, whereas myostatin expression was markedly increased in cells from CTRL and OA patients, suggesting the existence of an imbalance between BMP-2 and myostatin pathways (Tarantino et al, 2020)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
