Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers

ABSTRACT Microgravity exposure affects both tissues and cells, and, in this regard, one of the most affected targets is the skeletal muscle system due to the significant loss of bone and muscle mass leading to osteoporosis and sarcopenia, respectively. Several efforts are underway to counteract the...

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Main Authors: Lorenzo Sanesi, Roberta Zerlotin, Alessio Campiolo, Angela Oranger, Manuela Dicarlo, Clelia Suriano, Ameneh Ghadiri, Graziana Colaianni, Maria Grano, Sara Tavella, Silvia Colucci
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:FASEB BioAdvances
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Online Access:https://doi.org/10.1096/fba.2025-00085
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author Lorenzo Sanesi
Roberta Zerlotin
Alessio Campiolo
Angela Oranger
Manuela Dicarlo
Clelia Suriano
Ameneh Ghadiri
Graziana Colaianni
Maria Grano
Sara Tavella
Silvia Colucci
author_facet Lorenzo Sanesi
Roberta Zerlotin
Alessio Campiolo
Angela Oranger
Manuela Dicarlo
Clelia Suriano
Ameneh Ghadiri
Graziana Colaianni
Maria Grano
Sara Tavella
Silvia Colucci
author_sort Lorenzo Sanesi
collection DOAJ
description ABSTRACT Microgravity exposure affects both tissues and cells, and, in this regard, one of the most affected targets is the skeletal muscle system due to the significant loss of bone and muscle mass leading to osteoporosis and sarcopenia, respectively. Several efforts are underway to counteract the effects of microgravity, and recent studies on irisin, a myokine with anabolic effects on the musculoskeletal system, have shown promising results. Due to the practical challenges of conducting experiments in actual microgravity, different devices generating a simulated microgravity condition on Earth have been developed. Here, we exposed myoblasts, osteoblasts, osteocytes to a random position machine (RPM) for five days to assess microgravity effect on the expression of key differentiation factors in cells untreated or treated with irisin. In myoblasts (C2C12), exposure to RPM led to increased expression of early myogenesis maker genes Pax7 (p = 0.0016), Myf5 (p = 0.0005) and MyoD (p = 0.0009). Irisin treatment in the last 8 h of RPM cultures prevented these increases by returning Pax7 (p = 0.0008) and MyoD (p = 0.01) to control values, and only partially Myf5. In bone cells, exposure to RPM for 5 days showed no effect in osteoblasts (MC3T3) but decreased the expression of Pdpn (p = 0.0285) and Dmp‐1 (p = 0.0423) genes in osteocytes (MLO‐Y4). Irisin treatment completely prevented the decline in Pdpn (p = 0.293) and Dmp‐1 (p = 0.0339) levels. Overall, our data showed that the impact of RPM exposure keeps myoblasts and osteocytes in a proliferative state, and irisin treatment restores them to their baseline biological condition, suggesting that irisin can counteract the changes induced by simulated microgravity.
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spelling doaj-art-ec5705fe98b54f6bbd171f8e1eb364ae2025-08-20T03:56:41ZengWileyFASEB BioAdvances2573-98322025-07-0177n/an/a10.1096/fba.2025-00085Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation MarkersLorenzo Sanesi0Roberta Zerlotin1Alessio Campiolo2Angela Oranger3Manuela Dicarlo4Clelia Suriano5Ameneh Ghadiri6Graziana Colaianni7Maria Grano8Sara Tavella9Silvia Colucci10Department of Clinical and Experimental Medicine University of Foggia Foggia ItalyDepartment of Precision and Regenerative Medicine and Ionian Area University of Bari Bari ItalyCellular Oncology Unit IRCCS Ospedale Policlinico San Martino Genoa ItalyDepartment of Precision and Regenerative Medicine and Ionian Area University of Bari Bari ItalyDepartment of Precision and Regenerative Medicine and Ionian Area University of Bari Bari ItalyDepartment of Precision and Regenerative Medicine and Ionian Area University of Bari Bari ItalyCellular Oncology Unit IRCCS Ospedale Policlinico San Martino Genoa ItalyDepartment of Precision and Regenerative Medicine and Ionian Area University of Bari Bari ItalyDepartment of Precision and Regenerative Medicine and Ionian Area University of Bari Bari ItalyCellular Oncology Unit IRCCS Ospedale Policlinico San Martino Genoa ItalyDepartment of Translational Biomedicine and Neuroscience University of Bari Bari ItalyABSTRACT Microgravity exposure affects both tissues and cells, and, in this regard, one of the most affected targets is the skeletal muscle system due to the significant loss of bone and muscle mass leading to osteoporosis and sarcopenia, respectively. Several efforts are underway to counteract the effects of microgravity, and recent studies on irisin, a myokine with anabolic effects on the musculoskeletal system, have shown promising results. Due to the practical challenges of conducting experiments in actual microgravity, different devices generating a simulated microgravity condition on Earth have been developed. Here, we exposed myoblasts, osteoblasts, osteocytes to a random position machine (RPM) for five days to assess microgravity effect on the expression of key differentiation factors in cells untreated or treated with irisin. In myoblasts (C2C12), exposure to RPM led to increased expression of early myogenesis maker genes Pax7 (p = 0.0016), Myf5 (p = 0.0005) and MyoD (p = 0.0009). Irisin treatment in the last 8 h of RPM cultures prevented these increases by returning Pax7 (p = 0.0008) and MyoD (p = 0.01) to control values, and only partially Myf5. In bone cells, exposure to RPM for 5 days showed no effect in osteoblasts (MC3T3) but decreased the expression of Pdpn (p = 0.0285) and Dmp‐1 (p = 0.0423) genes in osteocytes (MLO‐Y4). Irisin treatment completely prevented the decline in Pdpn (p = 0.293) and Dmp‐1 (p = 0.0339) levels. Overall, our data showed that the impact of RPM exposure keeps myoblasts and osteocytes in a proliferative state, and irisin treatment restores them to their baseline biological condition, suggesting that irisin can counteract the changes induced by simulated microgravity.https://doi.org/10.1096/fba.2025-00085boneirisinmicrogravitymusclemyoblastsosteoblasts
spellingShingle Lorenzo Sanesi
Roberta Zerlotin
Alessio Campiolo
Angela Oranger
Manuela Dicarlo
Clelia Suriano
Ameneh Ghadiri
Graziana Colaianni
Maria Grano
Sara Tavella
Silvia Colucci
Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers
FASEB BioAdvances
bone
irisin
microgravity
muscle
myoblasts
osteoblasts
title Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers
title_full Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers
title_fullStr Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers
title_full_unstemmed Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers
title_short Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers
title_sort irisin prevents the effects of simulated microgravity on bone and muscle differentiation markers
topic bone
irisin
microgravity
muscle
myoblasts
osteoblasts
url https://doi.org/10.1096/fba.2025-00085
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