Physiological concentrations of retinoic acid suppress the osteoblastic differentiation of fetal rat calvaria cells in vitro

Ohishi, Keiji; Nishikawa, Shingo; Nagata, Toshihiko; Yamauchi, Noriyuki; Shinohara, Hiroyuki; Kido, Jun‐ichi; Ishida, Hiroshi

doi:10.1530/eje.0.1330335

Cited by 35 publications

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“…To explore changes in osteogenic differentiation and confirm the validity of our in vitro system by verifying the ubiquitous increase in osteopontin seen in other studies, we performed Northern blot analyses at 3, 12, 24, and 48 h for osteopontin on retinoic acid treated osteoblasts (Ohishi et al, 1995;Manji et al, 1998;Ahmed et al, 2000). Northern blot analyses demonstrated both a time and dose dependant induction of transcript for osteopontin following treatment with retinoic acid (Fig.…”

Section: Retinoic Acid Increases Osteopontin Expressionsupporting

confidence: 67%

“…Low-doses of retinoic acid (0.01 mM) have been demonstrated to increase levels of osteopontin and osteocalcin mRNA in fetal rat calvarial osteoblasts (Ohishi et al, 1995). Similarly, treatment of clonal preosteoblasts with pharmacologic amounts of retinoic acid has been shown to increase osteopontin transcript levels and enhance nuclear processing of primary mRNA transcripts (Manji et al, 1998).…”

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confidence: 99%

“…Similarly, treatment of clonal preosteoblasts with pharmacologic amounts of retinoic acid has been shown to increase osteopontin transcript levels and enhance nuclear processing of primary mRNA transcripts (Manji et al, 1998). While these data would seem to suggest that there is a direct relationship between retinoic acid level and osteoblast differentiation, the above studies have also demonstrated a decrease in alkaline phosphatase (AP) activity with both low and high-doses of retinoic acid, and decreases in osteocalcin transcription at highdoses (Ohishi et al, 1995;Ahmed et al, 2000). Thus, the actual effect that retinoic acid signaling has on osteoblast differentiation, proliferation, and matrix mineralization is unclear.…”

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High‐dose retinoic acid modulates rat calvarial osteoblast biology

Song

Nacamuli

Xia

et al. 2004

Journal Cellular Physiology

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Retinoic acid has been shown to adversely affect craniofacial development. Cleft palate and craniosynostosis are two examples of craniofacial defects associated with prenatal exposure to this agent. Although the effects of retinoic acid on cephalic neural crest-derived tissues have previously been studied, the specific effects of retinoic acid on the cellular biology of osteoblasts remain unclear. The purpose of this study was to analyze in detail the effects of pharmacologic doses of retinoic acid on the differentiation and proliferation of osteoblasts derived from an intramembranous source. Primary rat calvarial osteoblasts were established in culture and treated with 1 or 10 microM all-trans-retinoic acid. Retinoic acid treatment markedly increased expression of osteopontin up to 48 h after stimulation. Consistent with this early stage of differentiation, both mRNA and protein analysis of FGF receptor isoforms demonstrated a switch in predominance from fibroblast growth factor receptor 2 (fgfr2) to fgfr1. Analysis of PCNA protein confirmed inhibition of proliferation by retinoic acid. To determine whether these alterations in osteoblast biology would lead to increased differentiation, we examined short term [alkaline phosphatase (AP) activity] and long term (von Kossa staining) surrogates of bone formation in vitro. These assays confirmed that retinoic acid increased osteogenesis, with a 4-fold increase in bone nodule formation in cells treated with 10 microM retinoic acid after 28 days. Overall, our results demonstrated that pharmacologic doses of all-trans-retinoic acid decreased osteoblast proliferation and increased differentiation, suggesting that retinoic acid may effect craniofacial development by pathologically enhancing osteogenesis.

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Section: Retinoic Acid Increases Osteopontin Expressionsupporting

confidence: 67%

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confidence: 99%

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confidence: 99%

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High‐dose retinoic acid modulates rat calvarial osteoblast biology

Song

Nacamuli

Xia

et al. 2004

Journal Cellular Physiology

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“…The role of RA in osteoblastogenesis has been studied extensively in vitro and it has been shown to both promote and inhibit differentiation, as well as to drive bone matrix synthesis (Ahmed et al, 2000;Benayahu et al, 1994;Choong et al, 1993;Manji et al, 1998;Ohishi et al, 1995;Song et al, 2005;Wiper-Bergeron et al, 2007). Although variation between cell lines, the markers tested and experimental regimes might offer an explanation for these differing results, a clear consensus as to the role of RA has not emerged.…”

Section: Ra Signalling Is Required For Adipocyte Differentiation In Vivomentioning

confidence: 99%

Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways

Kelsh

Croucher

et al. 2010

Development

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SUMMARYAlthough the regulation of osteoblast and adipocyte differentiation from mesenchymal stem cells has been studied for some time, very little is known about what regulates their appearance in discrete regions of the embryo. Here we show that, as in other vertebrates, zebrafish osteoblasts and adipocytes originate in part from cephalic neural crest (CNC) precursors. We investigated the roles that the retinoic acid (RA) and Peroxisome proliferator-activated receptor gamma (Pparg) pathways play in vivo and found that both pathways act on CNC to direct adipocyte differentiation at the expense of osteoblast formation. In addition, we identify two distinct roles for RA in the osteoblast lineage: an early role in blocking the recruitment of osteoblasts and a later role in mature osteoblasts to promote bone matrix synthesis. These findings might help to increase our understanding of skeletal and obesityrelated diseases and aid in the development of stem cell-based regenerative therapies.KEY WORDS: Adipocyte, Osteoprogenitor, Osteoblast, Osteoblastogenesis, All trans retinoic acid, Bone, Cephalic neural crest, osterix (sp7), tcf7, Mesenchymal stem cell, Adipoprogenitor, Peroxisome proliferator-activated receptor gamma (Pparg), CCAAT/enhancer binding protein alpha (Cebpa), Runt-related transcription factor 2 (Runx2; Core binding factor a1), Zebrafish

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“…Hisada et al report that retinoic acid regulates the development of mesenchymal cells into osteoblasts and adipocytes [21]. Some authors suggest that retinoic acid stimulates osteoclastic bone resorption [22,23], while others report that retinoic acid has an inhibitory effect on osteoblastic cell proliferation [24].…”

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confidence: 99%

The Negative Impact of Selective Activation of Retinoic Acid Receptors on Bone Metabolism and Bone Mechanical Properties in Rats

et al. 2015

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hibitors, androgen deprivation therapy, heparin, calcineurin inhibitors and some chemotherapies are among the drugs increasing the risk of osteoporotic fractures [1].The mechanisms of the regulation of bone turnover involved in the etiology and pathology of osteoporosis seem to be very complex. Recent papers have revealed that various nuclear receptors are involved in the regulation of bone metabolism, its physiology and pathology. Many studies suggest Osteoporosis is defined as pathological bone microarchitecture making bones prone to low-energy fractures. In recent decades it has become one of the major health and socio-economic problems in many countries. Drug-induced osteoporosis is a significant health problem, as many drugs have deleterious effects on bone metabolism. Glucocorticoids, proton pump inhibitors, selective serotonin receptor inhibitors, thiazolidinediones, anticonvulsants, medroxyprogesterone acetate, aromatase in- AbstractBackground. Drug-induced osteoporosis is a significant health problem, as many drugs have deleterious effects on bone metabolism. Data from several studies concerning the influence of retinol on bone homeostasis are inconsistent. Objectives. The purpose of this study was to investigate the influence of tazarotene, a selective agonist of the retinoic acid receptor (RAR), on bone metabolism and bone mechanical properties in rats. Material and Methods. Sixteen male Wistar rats were assigned either to the group receiving tazarotene or to the control group. Serum biochemical markers of bone turnover (osteocalcin: OC, tartrate resistant acid phosphatase 5: TRACP5b, and osteoprotegerin: OPG) and the mechanical properties of bones were analyzed. Results. The mean Young's modulus was 24% higher (p < 0.05) in the control group than in the group receiving tazarotene. The stiffness of femur bones was 25% lower (p < 0.05) in rats receiving tazarotene. Flexural yield stress was slightly (2%) decreased in the tazarotene group, but the difference was not statistically significant. In the tazarotene group significantly lower serum concentration of bone turnover markers were obeserved (TRACP5b: 0.86 ± 0.30 ng/mL vs. 2.17 ± 0.67 ng/mL, OC: 7.77 ± 2.28 ng/mL vs. 13.04 ± 3.54 ng/mL and OPG: 0.09 ± 0.04 ng/mL vs. 0.27 ± 0.10) than in the control group. Conclusions. Tazarotene worsened bone mechanical properties and inhibited bone turnover in rats. These results suggest that tazarotene has a negative impact on bone metabolism and that it exerts osteoporotic activity (Adv Clin Exp Med 2016, 25, 2, 213-218).

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Physiological concentrations of retinoic acid suppress the osteoblastic differentiation of fetal rat calvaria cells in vitro

Cited by 35 publications

References 0 publications

High‐dose retinoic acid modulates rat calvarial osteoblast biology

High‐dose retinoic acid modulates rat calvarial osteoblast biology

Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways

The Negative Impact of Selective Activation of Retinoic Acid Receptors on Bone Metabolism and Bone Mechanical Properties in Rats

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