Antagonistic role of vitamin D3 and retinoic acid on the differentiation of chicken hematopoietic macrophages into osteoclast precursor cells.

Endocrinology ◽  
1995 ◽  
Vol 136 (1) ◽  
pp. 85-95 ◽  
Author(s):  
C Woods ◽  
C Domenget ◽  
F Solari ◽  
O Gandrillon ◽  
E Lazarides ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin D3 ◽  
Precursor Cells ◽  
Osteoclast Precursor

The Role of Transcriptional Coactivator TRAP220/MED1 in Nuclear Receptor-Mediated Myelomonocytic Differentiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2727-2727
Author(s):  
Mitsuhiro Ito ◽  
Norinaga Urahama ◽  
Akiko Sada ◽  
Kimikazu Yakushijin ◽  
Katsuya Yamamoto ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Precursor Cells ◽  
Mediator Complex ◽  
Dihydroxyvitamin D3 ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Hematopoietic Precursor

Abstract The TRAP/Mediator complex, the metazoan counterpart of the yeast Mediator complex, is master transcriptional regulatory complex composed of approximately 30 subunits. It was originally isolated as a thyroid hormone receptor (TR)-associated protein (TRAP) complex that mediates TR-activated transcription from DNA templates in vitro and probably acts in vivo after the action of other receptor-interacting coactivators involved in chromatin remodeling. The TRAP220/MED1 subunit of the TRAP/Mediator complex is proposed to act on a variety of major and specific biological events, including growth, differentiation and homeostasis, through physical interaction with nuclear receptors. The vitamin D receptor (VDR) and retinoic acid receptor (RAR), coupled with retinoid X receptor (RXR), are nuclear receptors which have important roles for monopoiesis and granulopoiesis, respectively. In this study, we present the functional role of TRAP220/MED1 in nuclear receptor-mediated monopoiesis and granulopoiesis. Since TRAP220 knockout (Trap220-/-) mice were mortalities during the early embryonic period before definitive hematopoiesis within the hepatic primordia becomes dominant, the function of TRAP220/MED1 in adult hematopoiesis was mostly unknown. However, these embryos appeared to have normal composition of nucleated erythroid cells. Therefore, the E9.0 yolk sac-derived hematopoietic precursor cells were used to differentiate into definitive hematopoietic colony forming units within the methylcellulose blood cell culture. The number of monocytic colonies (CFU-M) was significantly lower in knockouts than in wild type controls, while the numbers of other types of colonies (CFU-GEMM, CFU-GM, CFU-G and CFU-E) were comparable. Hence, TRAP220/MED1 appeared to be indispensable for optimal monocytic differentiation. Next, the HL-60 acute promyelocytic leukemia cells were used to elucidate directly and mechanistically the roles of TRAP220/MED1 in RAR- and VDR-dependent differentiation of the hematopoietic precursor cells into granulocytic and monocytic lineage cells. The expression of the TRAP220/MED1 subunit as well as other TRAP/Mediator subunits was induced when the cells were treated with their ligands, all-trans retinoic acid and 1,25-dihydroxyvitamin D3. Flow cytometric analyses showed that HL-60 cells, wherein TRAP220/MED1 was down-regulated, did not differentiate efficiently into monocytes and granulocytes by stimulation with 1,25-dihydroxyvitamin D3 and all-trans retinoic acid, correspondingly. The expression of direct target genes of VDR or RAR, as well as the differentiation marker genes, was low in the knockdown cells by stimulation with these ligands. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA)- and dimethylsulphoxide (DMSO)-mediated monocytic and myeloid differentiation, which bypasses nuclear receptor-mediated signaling pathways, was not affected in knockdown cells. Collectively, these results indicated an indispensable role of TRAP220/MED1 in the optimal VDR- and RAR-mediated myelomonocytic differentiation processes in mammalian hematopoiesis.

Long Term Follow-up of a Population of Low-Intermediate Risk Myelodisplastyc Syndrome Patients Treated with a Combination of Recombinant Erythropoietin, 13-Cis-Retinoic Acid and Dihydroxylated Vitamin D3 Confirms the Positive Role of Erythroid Response on Survival

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4968-4968
Author(s):  
Dario Ferrero ◽  
Elena Crisà ◽  
Antonella Darbesio ◽  
Cristina Foli ◽  
Valentina Giai ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Median Survival ◽  
Vitamin D3 ◽  
Recombinant Erythropoietin ◽  
Positive Role ◽  
Erythroid Response ◽  
Long Term Follow Up

Abstract Abstract 4968 In our previous paper (Ferrero et al, BJH 2009) we reported the treatment of 63 MDS patients (median age 75, 16 RAEB1, 47 non RAEB) with a combination of human recombinant erythropoietin (alfa or beta epoetin, 30–80000 U/ week, median 65000U/week), 13-cis-retinoic acid (20 mg day) and dihydroxylated vitamin D3 (1 ug day). Eleven of the 16 RAEB1 patients also received intermittent, low dose of 6-thioguanine. In spite of adverse prognostic factors for response to erythropoietin (all patients with Hb <9.5 g/dl, 70% transfusion dependent, 51% IPSS intermediate 1 or 2) 64% of non RAEB and 50% of RAEB1 displayed an erythroid response according to Cheson et al (Blood 2006). At previous evaluation (41 months of follow-up) a survival advantage was evident for non RAEB patients with erythroid response. Now we updated the casistic after 3 years from the previous evaluation. Median follow up for alive patients is now 64 months (5 months - 12 years). Median duration of erythroid response is now increased to 25 (2-88+) months for non RAEB and 6 (2.5-34.5+) months for RAEB1, 32.5% of responses in non RAEB patients have lasted more than 3 years. Twenty-nine/46 non RAEB and 14/16 RAEB1 patients died, with a median survival respectively of 57 and 15 months. Acute myeloid leukemia evolution occurred to 10 patients (5 RAEB1 and 5 non RAEB patients). Although the erythroid response did not correlate with known risk factors such as IPSS score, caryotype and transfusion requirement, it confirmed its positive prognostic role for survival in non RAEB patients (p 0.04, HR 2.06): median survival 71.5 months (range 12–150+) for responders, 30.6 months (range 5–149) for non responders. A trend towards a better survival for responder was also observed among RAEB1 patients (median survival 17 months for responders, 10 months for non responders), however, due to the low numbers of patients in this group, the difference was not statistically significant, even if border line (p 0.052, HR 2.52). In conclusion our long term follow-up confirmed the positive role of our combined treatment for response duration and survival in a group of non RAEB patients, most of them with unfavorable prognostic features.Figure 1.Overall survival of myelodisplastyc patients according to erythroid response: A. Non-RAEB patients:“___” responsive patients, “—” not responsive patients (p 0.04, HR 2.06) B. RAEB patients: “___” responsive patients, “—” not responsive patients (p 0.05, HR 2.52)Figure 1. Overall survival of myelodisplastyc patients according to erythroid response: A. Non-RAEB patients:“___” responsive patients, “—” not responsive patients (p 0.04, HR 2.06) B. RAEB patients: “___” responsive patients, “—” not responsive patients (p 0.05, HR 2.52) Disclosures: Off Label Use: The use of 13-cis retinoic acid and 1; 25(OH)2 vitamin D3 in myelodisplastyc syndrome is off-label. In our study we used that drugs in combination with erythropoietin as differentiative agents.

scholarly journals Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Wang ◽  
Lin Xu ◽  
Jiro Miura ◽  
Mithun Kumar Saha ◽  
Yume Uemura ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Muscle Development ◽  
Branchial Arch ◽  
Precursor Cells ◽  
Cellular Mechanisms ◽  
Pregnant Mice ◽  
Cranial Neural Crest Cells ◽  
Cranial Muscle

The first and second branchiomeric (branchial arch) muscles are craniofacial muscles that derive from branchial arch mesoderm. In mammals, this set of muscles is indispensable for jaw movement and facial expression. Defects during embryonic development that result in congenital partial absence of these muscles can have significant impact on patients’ quality of life. However, the detailed molecular and cellular mechanisms that regulate branchiomeric muscle development remains poorly understood. Herein we investigated the role of retinoic acid (RA) signaling in developing branchiomeric muscles using mice as a model. We administered all-trans RA (25 mg/kg body weight) to Institute of Cancer Research (ICR) pregnant mice by gastric intubation from E8.5 to E10.5. In their embryos at E13.5, we found that muscles derived from the first branchial arch (temporalis, masseter) and second branchial arch (frontalis, orbicularis oculi) were severely affected or undetectable, while other craniofacial muscles were hypoplastic. We detected elevated cell death in the branchial arch mesoderm cells in RA-treated embryos, suggesting that excessive RA signaling reduces the survival of precursor cells of branchiomeric muscles, resulting in the development of hypoplastic craniofacial muscles. In order to uncover the signaling pathway(s) underlying this etiology, we focused on Pitx2, Tbx1, and MyoD1, which are critical for cranial muscle development. Noticeably reduced expression of all these genes was detected in the first and second branchial arch of RA-treated embryos. Moreover, elevated RA signaling resulted in a reduction in Dlx5 and Dlx6 expression in cranial neural crest cells (CNCCs), which disturbed their interactions with branchiomeric mesoderm cells. Altogether, we discovered that embryonic craniofacial muscle defects caused by excessive RA signaling were associated with the downregulation of Pitx2, Tbx1, MyoD1, and Dlx5/6, and reduced survival of cranial myogenic precursor cells.

scholarly journals IL-6 Enhances Osteocyte-Mediated Osteoclastogenesis by Promoting JAK2 and RANKL Activity In Vitro

2017 ◽  
Vol 41 (4) ◽  
pp. 1360-1369 ◽  
Author(s):  
Qing Wu ◽  
Xiaokang Zhou ◽  
Danqing Huang ◽  
Yingchen JI ◽  
Feiwu Kang
Keyword(s):  
Protein Level ◽  
Orthognathic Surgery ◽  
Bone Remodelling ◽  
Precursor Cells ◽  
Osteoclast Precursor ◽  
Inflammatory Factors ◽  
Rankl Expression ◽  
Jak2 Inhibitor ◽  
Osteoclastic Differentiation

Background/Aims: Evidence suggests that IL-6 affects bone mass by modulating osteocyte communication towards osteoclasts. However, the mechanism by which IL-6 enhances osteocyte-mediated osteoclastogenesis is unclear. We aimed to investigate the inflammatory factors in serum after orthodontic surgery and their relationship between osteocytes and osteoclasts. Methods: Serum was obtained from 10 orthognathic surgery patients, and inflammatory factors were detected by ELISA. We treated the osteocyte-like cell line MLO-Y4 with recombinant mouse IL-6 and IL-6 receptor (IL-6R), and used quantitative RT-PCR and Western blotting to explore Receptor activator of nuclear factor-κB ligand (RANKL) expression at both the mRNA and protein level. MLO-Y4 cells were co-cultured with osteoclast precursor cells, and the formation of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. To explore the role of JAK2 in the osteocyte-mediated osteoclastogenesis, AG490, a JAK2 inhibitor, was used to inhibit the JAK2-STAT3 pathway in osteocytes. Results: In our study, we found that IL-6 and RANKL were stimulated in serum 3-7 days after orthognathic surgery. Therefore, IL-6 and IL-6 receptor enhanced the expression of RANKL at both the mRNA and protein level in MLO-Y4. Furthermore, when MLO-Y4 cells were co-cultured with osteoclast precursor cells, it significantly stimulated osteoclastogenesis. Our study indicated that osteocytes could promote osteoclastic differentiation and the formation of TRAP-positive multinucleated cells after stimulation with IL-6 and IL-6R. Our results also indicated that treatment with IL-6 and IL-6R increased RANKL mRNA expression and the RANKL/OPG expression ratio. Meanwhile, the phosphorylation of Janus kinase 2 (JAK2) and Signal transducer and activator of transcription (STAT3) also correlated with RANKL levels. Furthermore, we investigated the effects of a specific JAK2 inhibitor, AG490, on the expression of RANKL in osteocyte-like MLO-Y4 cells and osteocyte-mediated osteoclastogenesis. The results showed that AG490 inhibited (p)-JAK2 and RANKL expression. Osteoclastic differentiation was decreased after pretreatment in MLO-Y4 with mouse IL-6/IL-6R and AG490; therefore, we concluded that IL-6 increased osteocyte-mediated osteoclastic differentiation by activating JAK2 and RANKL. Conclusion: The effects of IL-6/il-6R and AG490 on osteocyte-mediated osteoclastogenesis contribute to our understanding of the role of inflammatory factors in the interaction between osteocytes and osteoclast precursors. IL-6 and RANKL are key factors for bone remodelling after the orthodontic surgery, and their roles in bone remodelling may be fundamental mechanisms accelerating tooth movement by orthodontic surgery.

SUBLINGUAL VITAMIN D3 DRUG THERAPY IN VITAMIN D DEFICIENCY PATIENTS AT PRAVARA RURAL HOSPITAL

2019 ◽  
pp. 18-20
Author(s):  
Sanjeeva Kumar Goud T ◽  
Rahul Kunkulol
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Serum Vitamin ◽  
Cross Sectional ◽  
Serum Vitamin D ◽  
Significant Difference ◽  
Before And After

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual route

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