Retinoic Acid Suppresses Interleukin 6 Production in Normal Human Osteoblasts

Ahmed, Nazish; Sammons, J.; Khokher, M. A.; Hassan, H. T.

doi:10.1006/cyto.1999.0588

Cited by 26 publications

(25 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protein is considered to be an indicator of osteoblast activity and is regarded as a marker of bone formation (20)(21)(22). Previous experimental studies have found that vitamin A hypervitaminosis decreases bone formation in rats (23), and that the retinol metabolite, retinoic acid, decreases production of alkaline phosphatase, osteocalcin, and interleukin-6 in human osteoblast cells, and simultaneously decreases differentiation of those cells (24). Thus, our results may indicate that retinol decreases bone formation in young men.…”

Section: Discussionsupporting

confidence: 50%

Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study

Högström

Nordström

2008

European Journal of Endocrinology

View full text Add to dashboard Cite

Context: The association between retinol and bone mineral density (BMD) in males after puberty has not been fully investigated previously. Objective: To investigate the association between retinol, retinol-binding protein-4 (RBP-4), BMD (g/cm 2 ), abdominal fat mass, and markers of bone metabolism in young men. Design: Longitudinal study. Participants: Seventy-eight healthy males with a mean age of 22.6G0.7 years at baseline. A follow-up was conducted in 73 of the participants 2.0G0.4 years later. Main outcome measures: Associations between serum concentrations of retinol and RBP-4, and BMD of the total body, lumbar spine, and hip, serum concentrations of osteocalcin, and carboxy terminal telopeptide of type 1 collagen (CTX), were investigated. Results: Both retinol and RBP-4 showed an inverse relationship with that of osteocalcin (rZK0.23 to K0.25, P!0.05). Levels of RBP-4 (rZ0.26, PZ0.02) and osteocalcin (rZK0.23, PZ0.04) were also related to abdominal fat mass, and the relationship between RBP-4, retinol, and osteocalcin disappeared after adjusting for this influence of abdominal fat mass. Neither retinol nor RBP-4 concentrations were associated with BMD at any site, CTX as baseline, or changes in BMD during the 2-year follow-up period. Levels of RBP-4 showed a strong association with levels of retinol (rZ0.61, P!0.001). Conclusion: We found a negative association between the bone formation marker osteocalcin with retinol and RBP-4. The association disappeared when adjusting for the influence of abdominal fat mass. Neither retinol nor RBP-4 were associated with peak BMD in young men. 158 765-770 European Journal of Endocrinology

show abstract

Section: Discussionsupporting

confidence: 50%

Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study

Högström

Nordström

2008

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Previous studies reported the effects of RA on the expression of osteoblastic markers and mineralization by using mouse, rat or human osteoblastic cell culture systems (Choong et al, 1993;Heath et al, 1989;Nakayama et al, 1990;Ng et al, 1985Ng et al, , 1988Ng et al, , 1989Oliva et al, 1993;Suzuki et al, 1993, Thein andLotan, 1982;Varghese et al, 1994;Zhou et al, 1991). However, these results are conflicting; for example, ALP activity was induced by RA in the culture of rat osteoblastic cell lines, RCT-1,3 (Heath et al, 1989) and UMR-201 (Choong et al, 1993;Ng et al, 1988Ng et al, , 1989Zhou et al, 1991), as well as in murine osteoblastic cell lines, BFO (Suzuki et al, 1993) and MC3T3-E1 (Nakayama et al, 1990), whereas it was inhibited in another mouse cell line (Cohen-Tanugi and Forest, 1998) and primary human osteoblastic cells (Ahmed et al, 2000). As for the regulation of other osteoblastic markers, including =1(I)Col, OPN (Varghese et al, 1994;Zhou et al, 1991), ON (Ng et al, 1989) and OC (Ahmed et al, 2000;CohenTanugi and Forest, 1998;Oliva et al, 1993), some studies also reported conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…However, these results are conflicting; for example, ALP activity was induced by RA in the culture of rat osteoblastic cell lines, RCT-1,3 (Heath et al, 1989) and UMR-201 (Choong et al, 1993;Ng et al, 1988Ng et al, , 1989Zhou et al, 1991), as well as in murine osteoblastic cell lines, BFO (Suzuki et al, 1993) and MC3T3-E1 (Nakayama et al, 1990), whereas it was inhibited in another mouse cell line (Cohen-Tanugi and Forest, 1998) and primary human osteoblastic cells (Ahmed et al, 2000). As for the regulation of other osteoblastic markers, including =1(I)Col, OPN (Varghese et al, 1994;Zhou et al, 1991), ON (Ng et al, 1989) and OC (Ahmed et al, 2000;CohenTanugi and Forest, 1998;Oliva et al, 1993), some studies also reported conflicting results. In this study, we showed that RA inhibited ALP activity of human osteoblastic cells, depending on the differentiation stage.…”

Section: Discussionmentioning

confidence: 99%

Phase-independent Inhibition by Retinoic Acid of Mineralization Correlated with Loss of Tetranectin Expression in a Human Osteoblastic Cell Line.

Iba¹,

Chiba

Yamashita³

et al. 2001

Cell Struct. Funct.

View full text Add to dashboard Cite

ABSTRACT. We have recently reported that retinoic acid inhibits dexamethasone-induced alkaline phosphatase activity and mineralization in human osteoblastic cell line SV-HFO. In this study, we show that this inhibitory effect on alkaline phosphatase activity depends on the stage of cell differentiation; however, expression of tetranectin, which is a recently reported bone matrix protein, was completely inhibited by treatment with retinoic acid, irrespective of the stage of cell differentiation. Similarly, mineral deposit formation in SV-HFO cells was phase-independently inhibited by retinoic acid. To our knowledge, this is the first report that retinoic acid downregulates the tetranectin expression in human osteoblastic cells independent of the stage of cell differentiation, and is correlated with inhibition of mineralization. Key words: retinoic acid(RA)/tetranectin(TET)/mineralization/human/osteoblastRetinoids have a wide variety of effects on vertebrate embryogenesis and development, cellular differentiation, proliferation, and apoptosis, as well as homeostasis via two classes of ligand-dependent transactivators: the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), both of which are members of the nuclear receptor superfamily

show abstract

“…ELISA kits were used for the in vitro quantitative determination of human IL-6, sgp130 (R&D Systems; Oxon, UK; http://www.rndsystems.com) and IL-11 concentrations (Diaclone; Boldon, UK; http://www.diaclone.com), in the supernatant of control and RA-treated four-week bone marrow cultures as previously described [13]. RA-treated and control supernatant samples, together with standards and the subsequent addition of biotinylated antibody of IL-6 or sgp130, were incubated for 2 h in a 96-well microtitre plate precoated with an antihuman IL-6 or gp130 (R&D Systems) at room temperature.…”

Section: Quantitative Enzyme-linked Immunosorbent Assay (Elisa) Measumentioning

confidence: 99%

“…Therefore, the present study was performed to examine any similar inhibitory effect of 1 µM RA on the CAFC in long-term human bone marrow cultures and to explore possible mechanism(s) mediating such an inhibitory effect. RA has been shown to inhibit interleukin 6 (IL-6) production in several normal and malignant human cell types including B-lymphocytes, osteoblasts, lung fibroblasts, keratinocytes, epidermoid carcinoma, Kaposi's sarcoma and myeloma cells [10][11][12][13][14][15][16][17][18][19][20]. Hence, the present study investigated the effect of RA on IL-6 and IL-11 production, as well as their soluble signal transducing receptor gp130 (sgp 130) from normal human bone marrow stroma.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms Mediating the Inhibitory Effect of All‐Trans Retinoic Acid on Primitive Hematopoietic Stem Cells in Human Long‐Term Bone Marrow Culture

et al. 2000

View full text Add to dashboard Cite

All-trans retinoic acid (RA) has generally been found to stimulate late committed (colony-forming unitgranulocyte, macrophage [CFU-GM]) and inhibit early (CFU-Blast) normal human myeloid progenitor cells. The present study provides the first evidence that the pharmacological concentration of 1 µM RA, exerts an inhibitory effect on the proliferation of functional human primitive hemopoietic stem cells (cobblestone area-forming cell [CFAC]) in long-term bone marrow cultures. Treatment of four-week confluent bone marrow culture with 1 µM RA for five days significantly reduced week 4 CAFC from 88 ± 10 in control cultures to only 52 ± 12 per 10 5 cells, p < 0.01. Quantitative enzyme-linked immunosorbent assay measurement of interleukin 6 (IL-6) and IL-11 produced from the fourweek bone marrow stroma culture revealed only a slight and moderate increase of IL-6 and IL-11 production after treatment with RA. On the other hand, treatment with RA profoundly increased the soluble receptor gp130 released from the four-week bone marrow stroma by 7.5-fold from only 145 ± 2.1 pg per ml in control cultures to 1,069.9 ± 3.8 pg per ml in RA-treated cultures. A similar marked increase in the soluble adhesion molecules ICAM-1, and to a lesser extent VCAM-1, released from the four-week bone marrow stroma was observed after RA treatment.IL-6 has been implicated in the inhibitory effect of RA in several human hemopoietic and nonhemopoietic cells. The common transducing signal chain gp130, for all receptors of the IL-6 cytokine family, is expressed in most primitive human hemopoietic CD34 + cells and its signaling was shown to synergize with other hemopoietic cytokines to expand primitive human hemopoietic stem cells. Recently, soluble gp130 was shown to be a natural potent antagonist of the human IL-6 cytokine family by binding the ligand and thereby reducing its bioavailability.The profound and rapid 7.5-fold increase in the natural antagonist of human IL-6 cytokine family after RA treatment could abrogate the gp130 signaling required for proliferation and/or expansion of human primitive hemopoietic stem cells and lead to the observed inhibitory effect of RA on CAFC. Both adhesion molecules VCAM-1 and ICAM-1 mediate human hemopoietic stem cell adhesion to marrow stroma. The present significant increase in the soluble form of these adhesion molecules after RA treatment could exert a significant antagonist effect on their function and hence may impair CAFC adhesion to marrow stroma.In conclusion, the RA inhibitory effect on the proliferation of primitive human hemopoietic stem cells could be mediated through: A) an impaired hemopoietic stem cell adhesion due to the significant increase in soluble adhesion molecules released from the marrow stroma after RA treatment, and B) a significantly reduced gp130 signaling that is necessary for stem cell proliferation due to the natural antagonistic effect of the profoundly increased level of soluble gp130 released from the marrow stroma after treatment with RA.

show abstract

Retinoic Acid Suppresses Interleukin 6 Production in Normal Human Osteoblasts

Cited by 26 publications

References 22 publications

Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study

Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study

Phase-independent Inhibition by Retinoic Acid of Mineralization Correlated with Loss of Tetranectin Expression in a Human Osteoblastic Cell Line.

Mechanisms Mediating the Inhibitory Effect of All‐Trans Retinoic Acid on Primitive Hematopoietic Stem Cells in Human Long‐Term Bone Marrow Culture

Contact Info

Product

Resources

About