title: Evidence for Vitamin D Receptor Expression and Direct Effects of 1α,25(OH)2D3 in Human Skeletal Muscle Precursor Cells.
abstract: Presence of the vitamin D receptor and direct effects of vitamin D on the proliferation and differentiation of muscle precursor cells have been demonstrated in animal models. However, the effects and mechanisms of vitamin D actions in human skeletal muscle, and the presence of the vitamin D receptor in human adult skeletal muscle, remain to be established. Here, we investigated the role of vitamin D in human muscle cells at various stages of differentiation. We demonstrate that the components of the vitamin D-endocrine system are readily detected in human muscle precursor cells but are low to nondetectable in adult skeletal muscle and that human muscle cells lack the ability to convert the inactive vitamin D-metabolite 25-hydroxy-vitamin D3 to the active 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3). In addition, we show that 1α,25(OH)2D3 inhibits myoblast proliferation and differentiation by altering the expression of cell cycle regulators and myogenic regulatory factors, with associated changes in forkhead box O3 and Notch signaling pathways. The present data add novel information regarding the direct effects of vitamin D in human skeletal muscle and provide functional and mechanistic insight to the regulation of myoblast cell fate decisions by 1α,25(OH)2D3.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Olsson
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Amarjit
authors.initials: A
authors.lastname: Saini
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Strömberg
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Seher
authors.initials: S
authors.lastname: Alam
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Lilja
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Rullman
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gustafsson
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D006900:Hydroxylation; D008297:Male; D009000:Monocytes / Q000378:metabolism; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D018167:Receptors, Calcitriol; D051880:Receptors, Notch; C579457:VDR protein, human; D002117:Calcitriol; D002112:Calcifediol