Role of Myostatin in Muscle Degeneration by Random Positioning Machine Exposure: An in vitro Study for the Treatment of Sarcopenia

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.

Exposure to Random Positioning Machine Alters the Mineralization Process and PTX3 Expression in the SAOS-2 Cell Line

“…The identification of the underlying molecular mechanisms is crucial for the development of strategies not only to counteract this phenomenon, but also to guarantee astronauts an optimal and rapid recovery after space missions. Interestingly, the physiological changes observed in astronauts exposed to spaceflight are also commonly found in the elderly, suggesting that weightlessness may reproduce the pathophysiological changes that characterize the aging process [ 29 , 30 , 31 ]. Therefore, studying the effects induced by weightlessness may help to counteract the progression of diseases affecting the geriatric population.…”

Sarcopenia and bone health: new acquisitions for a firm liaison

“…25 Furthermore, the expression pattern of myostatin has been proposed to play a key role in load-free muscle damage, as treatment with anti-myostatin antibodies was able to counteract the negative effect induced by RPM exposure in primary cultures of human satellite cells, restoring muscle morphology and function. 26…”

“…The protein belongs to the TGF-β family and is produced by skeletal muscle; interacting with its receptor activin IIB (ActRIIB) leads to a decrease in myoblast proliferation and an increase in muscle degradation. 26 The ActRIIB receptor is also found with osteoblasts and chondroblasts and its activation appears to be involved in bone remodelling. Its role has led researchers in inhibiting myostatin pathways as drug therapy for OS.…”

Osteosarcopenia and Long-COVID: a dangerous combination

“…56 The pathogenesis of osteosarcopenia is multifactorial, with several mechanical, biochemical, genetic and lifestyle factors all contributing to the regulation of the muscle-bone unit. 57 The balance between these factors is crucial, and a disruption of it leads to innumerable bone and muscle risks and complications, causing deterioration of bone microarchitecture in association with the loss of muscle mass, strength and function. [58][59][60] In this context, SARS-CoV-2 infection has been suggested to amplify the effects of aging on the musculoskeletal system by aggravating the osteosarcopenic state.…”