Immediate effects of retinoic acid on gene expression in primary murine osteoblasts
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Immediate effects of retinoic acid on gene expression in primary murine osteoblasts. / Yorgan, Timur A; Heckt, Timo; Rendenbach, Carsten; Helmis, Christina; Seitz, Sebastian; Streichert, Thomas; Amling, Michael; Schinke, Thorsten.
In: J BONE MINER METAB, Vol. 34, No. 2, 01.03.2016, p. 161-70.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Immediate effects of retinoic acid on gene expression in primary murine osteoblasts
AU - Yorgan, Timur A
AU - Heckt, Timo
AU - Rendenbach, Carsten
AU - Helmis, Christina
AU - Seitz, Sebastian
AU - Streichert, Thomas
AU - Amling, Michael
AU - Schinke, Thorsten
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Consistent with clinical observations demonstrating that hypervitaminosis A is associated with increased skeletal fracture risk, we have previously found that dietary retinol deprivation partially corrects the bone mineralization defects in a mouse model of X-linked hypophosphatemic rickets. That retinol-dependent signaling pathways impact the skeleton is further supported by various findings demonstrating a negative influence of retinoic acid (RA) on bone-forming osteoblasts. We hypothesized that RA would directly regulate the expression of specific target genes in osteoblasts, and we aimed to identify these by genome-wide expression analyses. Here we show that high dietary retinol intake in mice causes low bone mass associated with increased osteoclastogenesis and decreased osteoblastogenesis, but intact bone matrix mineralization. We additionally found that short-term treatment of primary osteoblasts with RA causes a rapid induction of specific genes involved in either retinol-dependent signaling (i.e. Rara, Crabp2) or skeletal remodeling (i.e. Twist2, Tnfsf11). In contrast, neither expression of established osteoblast differentiation markers nor the proliferation rate was immediately affected by RA administration. Collectively, our data suggest that the negative effects of vitamin A on skeletal integrity are explainable by an immediate influence of RA signaling on specific genes in osteoblasts that in turn influence bone remodeling.
AB - Consistent with clinical observations demonstrating that hypervitaminosis A is associated with increased skeletal fracture risk, we have previously found that dietary retinol deprivation partially corrects the bone mineralization defects in a mouse model of X-linked hypophosphatemic rickets. That retinol-dependent signaling pathways impact the skeleton is further supported by various findings demonstrating a negative influence of retinoic acid (RA) on bone-forming osteoblasts. We hypothesized that RA would directly regulate the expression of specific target genes in osteoblasts, and we aimed to identify these by genome-wide expression analyses. Here we show that high dietary retinol intake in mice causes low bone mass associated with increased osteoclastogenesis and decreased osteoblastogenesis, but intact bone matrix mineralization. We additionally found that short-term treatment of primary osteoblasts with RA causes a rapid induction of specific genes involved in either retinol-dependent signaling (i.e. Rara, Crabp2) or skeletal remodeling (i.e. Twist2, Tnfsf11). In contrast, neither expression of established osteoblast differentiation markers nor the proliferation rate was immediately affected by RA administration. Collectively, our data suggest that the negative effects of vitamin A on skeletal integrity are explainable by an immediate influence of RA signaling on specific genes in osteoblasts that in turn influence bone remodeling.
U2 - 10.1007/s00774-015-0666-2
DO - 10.1007/s00774-015-0666-2
M3 - SCORING: Journal article
C2 - 25956707
VL - 34
SP - 161
EP - 170
JO - J BONE MINER METAB
JF - J BONE MINER METAB
SN - 0914-8779
IS - 2
ER -