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METTL21C: From GWAS to in vitro function in skeletal muscle cells
Author(s) -
Huang Jian,
Hsu YiHsiang,
Mo Chenglin,
Abreu Eduardo,
Karasik David,
Brotto Marco
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.942.5
Subject(s) - myogenesis , c2c12 , myocyte , skeletal muscle , biology , gene silencing , sarcopenia , phenotype , small interfering rna , transfection , microbiology and biotechnology , gene , genetics , endocrinology
Sarcopenia and osteoporosis are among the most serious and costly public health problems and often occur concurrently. Bivariate genome‐wide association studies (GWAS) identified METTL21C as a candidate gene for bone‐muscle pleotropy. Intriguingly, METTL21C is highly expressed in skeletal muscles, but the roles of this gene are largely unknown. We used siRNAs to silence METTL21C in C2C12 myoblasts to study its function on myogenesis. After 24h of transfection, real‐time PCR revealed that METTL21C expression was reduced by 30–40% in the siRNA‐treated cells. Two days after the onset of differentiation, a significantly reduced number of fusing myocytes was observed. At day 4, early myotubes were clearly observed in the control group but not in the siRNA‐treated cells. By day 7, fully matured and developed myotubes were observed in the control but not in the siRNA‐treated cells. Silencing of this relatively unknown gene led to a striking phenotype of fewer, shorter and smaller myotubes. These results suggest that METTL21C plays an important role in skeletal muscle cell differentiation. We are now performing similar studies in MLO‐Y4 osteocytes and plan to expand these studies to include biochemical and functional analyses to determine and validate its pleiotropic effects in in‐vitro models of bone and muscle research. Support: NIH‐NIA P01 AG039355 and Missouri Life Sci. Res. Board (MB) and R01 AR057118 (DK)