Related Experiment Video
Updated: Jan 26, 2026
Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans
Published on: February 16, 2017
Clusterin silencing restores myoblasts viability and down modulates the inflammatory process in osteoporotic disease
S Pucci1, C Greggi2,3, C Polidoro4
1Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier 1, 00133, Rome, Italy. sabina.pucci@uniroma2.it.
Background:
Targeting new molecular pathways leading to Osteoporosis (OP) and Osteoarthritis (OA) is a hot topic for drug discovery. Clusterin (CLU) is a glycoprotein involved in inflammation, proliferation, cell death, neoplastic disease, Alzheimer disease and aging. The present study focuses on the expression and the role of CLU in influencing the decrease of muscle mass and fiber senescence in OP-OA condition.
Methods:
Vastus lateralis muscle biopsies were collected from 20 women with OP undergoing surgery for fragility hip fracture and 20 women undergoing arthroplasty for hip osteoarthritis.
Results:
We found an overexpression of CLU in degenerated fibers in OP closely correlated with interleukin 6 (IL6) and histone H4 acetylation level. Conversely, in OA muscle tissues we observed a weak expression of CLU but no nuclear histone H4 acetylation. Ex vivo studies on isolated human myoblasts confirmed CLU overexpression in OP as compared to OA (p < 0.001). CLU treatment of isolated OP and OA myoblasts showed: modulation of proliferation, morphological changes, increase of histone H4 acetylation and induction of myogenin (MYOG) activation in OP myoblast only. In OP condition, functional knockdown of CLU by siRNA restores proliferative myoblasts capability and tissue damage repair, carried out by an evident upregulation of Transglutaminase 2 (TGM2). We also observed downmodulation of CX3CR1 expression with consequent impairing of the inflammatory infiltrate recruitment.
Conclusions:
Results obtained suggest a potential role of CLU in OP by influencing myoblasts terminal differentiation, epigenetic regulation of muscle cell differentiation and senescence. Moreover, CLU silencing points out its role in the modulation of tissue damage repair and inflammation, proposing it as a new diagnostic marker for muscle degeneration and a potential target for specific therapeutic intervention in OP related sarcopenia.
Insights
Clusterin (CLU) is overexpressed in osteoporosis, driving muscle degeneration and senescence. Silencing CLU restores muscle repair and reduces inflammation, identifying it as a therapeutic target for osteoporosis-related sarcopenia.
Area of Science:
- Biochemistry
- Molecular Biology
- Gerontology
Background:
- Clusterin (CLU), a glycoprotein, is implicated in aging and various diseases.
- Investigating CLU's role in muscle mass decline and fiber senescence in Osteoporosis (OP) and Osteoarthritis (OA) is crucial for drug discovery.
- Focus on CLU's expression and function in the context of OP-OA muscle degeneration.
Purpose of the Study:
- To investigate the expression and role of Clusterin (CLU) in muscle degeneration associated with Osteoporosis (OP) and Osteoarthritis (OA).
- To explore CLU's influence on myoblast proliferation, differentiation, senescence, and tissue repair in OP and OA.
- To assess CLU as a potential diagnostic marker and therapeutic target for OP-related sarcopenia.
Main Methods:
- Analysis of vastus lateralis muscle biopsies from women with OP and OA.
- Ex vivo studies on isolated human myoblasts, including CLU treatment and siRNA-mediated knockdown.
- Assessment of CLU expression, histone H4 acetylation, myogenin (MYOG) activation, Transglutaminase 2 (TGM2), and CX3CR1 expression.
Main Results:
- CLU was overexpressed in degenerated muscle fibers in OP, correlated with IL6 and histone H4 acetylation.
- CLU treatment modulated myoblast proliferation and differentiation, inducing MYOG activation in OP myoblasts.
- CLU knockdown in OP myoblasts restored proliferation, enhanced tissue repair via TGM2 upregulation, and reduced inflammation by downregulating CX3CR1.
Conclusions:
- CLU plays a significant role in OP-related muscle degeneration by influencing myoblast differentiation, epigenetic regulation, and senescence.
- CLU silencing demonstrates its potential in modulating tissue repair and inflammation.
- CLU is proposed as a novel diagnostic marker for muscle degeneration and a therapeutic target for OP-related sarcopenia.
Related Concept Videos
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:21Inflammatory Bowel Disease V: Surgical Management
Here are some common surgical interventions for IBD:
01:19Restorative Care
01:29Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...
01:13Formation of Muscle Fibers from Myoblasts
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...