title: The effect of parathyroid hormone on the uptake and retention of 25-hydroxyvitamin D in skeletal muscle cells.
abstract: Data from our studies, and those of others, support the proposal that there is a role for skeletal muscle in the maintenance of vitamin D status. We demonstrated that skeletal muscle is able to internalise extracellular vitamin D binding protein, which then binds to actin in the cytoplasm, to provide high affinity binding sites which accumulate 25-hydroxyvitamin D3(25(OH)D3) [1]. This study investigated the concentration- and time-dependent effects of parathyroid hormone (PTH) on the capacity of muscle cells to take up and release3H-25(OH)D3. Uptake and retention studies for3H-25(OH)D3were carried out with C2C12 cells differentiated into myotubes and with primary mouse muscle fibers as described [1]. The presence of PTH receptors on mouse muscle fibers was demonstrated by immunohistochemistry and PTH receptors were detected in differentiated myotubes, but not myoblasts, and on muscle fibers by Western blot. Addition of low concentrations of vitamin D binding protein to the incubation media did not alter uptake of 25(OH)D3. Pre-incubation of C2 myotubes or primary mouse muscle fibers with PTH (0.1 to 100 pM) for 3h resulted in a concentration-dependent decrease in 25(OH)D3uptake after 4 or 16h. These effects were significant at 0.1 or 1pM PTH (p<0.001) and plateaued at 10pM, with 25(OH)D3uptake reduced by over 60% (p<0.001) in both cell types. In C2 myotubes, retention of 25(OH)D3was decreased after addition of PTH (0.1 to 100pM) in a concentration-dependent manner by up to 80% (p<0.001) compared to non-PTH treated-C2 myotubes. These data show that muscle uptake and retention of 25(OH)D3are modulated by PTH, a physiological regulator of mineral homeostasis, but the cell culture model may not be a comprehensive reflection of vitamin D homeostatic mechanisms in whole animals.
authors.affiliation: Physiology, School of Medical Sciences, Sydney Medical School, Australia; Bosch Institute for Medical Research, Australia; College of Sustainability Sciences and Humanities- Zayed University, Abu Dhabi, United Arab Emirates.
authors.forename: M
authors.initials: M
authors.lastname: Abboud
authors.affiliation: Physiology, School of Medical Sciences, Sydney Medical School, Australia; Bosch Institute for Medical Research, Australia.
authors.forename: M S
authors.initials: MS
authors.lastname: Rybchyn
authors.affiliation: Sydney School of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Physiology, School of Medical Sciences, Sydney Medical School, Australia; Bosch Institute for Medical Research, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Physiology, School of Medical Sciences, Sydney Medical School, Australia; Bosch Institute for Medical Research, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Gordon-Thomson
authors.affiliation: Physiology, School of Medical Sciences, Sydney Medical School, Australia; Bosch Institute for Medical Research, Australia.
authors.forename: T C
authors.initials: TC
authors.lastname: Brennan-Speranza
authors.affiliation: Bosch Institute for Medical Research, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Cole
authors.affiliation: Sydney School of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Greenfield
authors.affiliation: Sydney School of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: D R
authors.initials: DR
authors.lastname: Fraser
authors.affiliation: Physiology, School of Medical Sciences, Sydney Medical School, Australia; Bosch Institute for Medical Research, Australia. Electronic address: rebecca.mason@sydney.edu.au.
authors.forename: R S
authors.initials: RS
authors.lastname: Mason
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D008807:Mice, Inbred BALB C; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D010281:Parathyroid Hormone / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D010281:Parathyroid Hormone; D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: 25-Hydroxvitamin D; Muscle; Myotubes; Parathyroid hormone; Vitamin D status