TY - JOUR
T1 - Circadian mechanisms in murine and human bone marrow mesenchymal stem cells following dexamethasone exposure
AU - Wu, Xiying
AU - Yu, Gang
AU - Parks, Helen
AU - Hebert, Teddi
AU - Goh, Brian C.
AU - Dietrich, Marilyn A.
AU - Pelled, Gadi
AU - Izadpanah, Reza
AU - Gazit, Dan
AU - Bunnell, Bruce A.
AU - Gimble, Jeffrey M.
PY - 2008/5
Y1 - 2008/5
N2 - A core group of regulatory factors control circadian rhythms in mammalian cells. While the suprachiasmatic nucleus in the brain serves as the central core circadian oscillator, circadian clocks also exist within peripheral tissues and cells. A growing body of evidence has demonstrated that > 20% of expressed mRNAs in bone and adipose tissues oscillate in a circadian manner. The current manuscript reports evidence of the core circadian transcriptional apparatus within primary cultures of murine and human bone marrow-derived mesenchymal stem cells (BMSCs). Exposure of confluent, quiescent BMSCs to dexamethasone synchronized the oscillating expression of the mRNAs encoding the albumin D binding protein (dbp), brain-muscle arnt-like 1 (bmal1), period 3 (per3), rev-erb α (Rev A), and rev-erb β (Rev B). The genes displayed a mean oscillatory period of 22.2 to 24.3 h. The acrophase or peak expression of mRNAs encoding "positive" (bmal1) and "negative" (per3) components of the circadian regulatory apparatus were out of phase with each other by ~ 8-12 h, consistent with in vivo observations. In vivo, phosphyrylation by glycogen synthase kinase 3β (GSK3β) is known to regulate the turnover of per3 and components of the core circadian regulatory apparatus. In vitro addition of lithium chloride, a GSK3β inhibitor, significantly shifted the acrophase of all genes by 4.2-4.7 h oscillation in BMSCs; however, only the male murine BMSCs displayed a significant increase in the length of the period of oscillation. We conclude that human and murine BMSCs represent a valid in vitro model for the analysis of circadian mechanisms in bone metabolism and stem cell biology.
AB - A core group of regulatory factors control circadian rhythms in mammalian cells. While the suprachiasmatic nucleus in the brain serves as the central core circadian oscillator, circadian clocks also exist within peripheral tissues and cells. A growing body of evidence has demonstrated that > 20% of expressed mRNAs in bone and adipose tissues oscillate in a circadian manner. The current manuscript reports evidence of the core circadian transcriptional apparatus within primary cultures of murine and human bone marrow-derived mesenchymal stem cells (BMSCs). Exposure of confluent, quiescent BMSCs to dexamethasone synchronized the oscillating expression of the mRNAs encoding the albumin D binding protein (dbp), brain-muscle arnt-like 1 (bmal1), period 3 (per3), rev-erb α (Rev A), and rev-erb β (Rev B). The genes displayed a mean oscillatory period of 22.2 to 24.3 h. The acrophase or peak expression of mRNAs encoding "positive" (bmal1) and "negative" (per3) components of the circadian regulatory apparatus were out of phase with each other by ~ 8-12 h, consistent with in vivo observations. In vivo, phosphyrylation by glycogen synthase kinase 3β (GSK3β) is known to regulate the turnover of per3 and components of the core circadian regulatory apparatus. In vitro addition of lithium chloride, a GSK3β inhibitor, significantly shifted the acrophase of all genes by 4.2-4.7 h oscillation in BMSCs; however, only the male murine BMSCs displayed a significant increase in the length of the period of oscillation. We conclude that human and murine BMSCs represent a valid in vitro model for the analysis of circadian mechanisms in bone metabolism and stem cell biology.
KW - Bone marrow mesenchymal stem cells
KW - Circadian
KW - Dexamethasone
KW - Lithium chloride
KW - Rev-erb α
UR - http://www.scopus.com/inward/record.url?scp=41949095284&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2007.12.226
DO - 10.1016/j.bone.2007.12.226
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C2 - 18302991
AN - SCOPUS:41949095284
SN - 8756-3282
VL - 42
SP - 861
EP - 870
JO - Bone
JF - Bone
IS - 5
ER -