Pleiotropic Effects of Vitamin D on Osteoblast Gene Expression Are Related to the Proliferative and Differentiated State of the Bone Cell Phenotype: Dependency upon Basal Levels of Gene Expression, Duration of Exposure, and Bone Matrix Competency in Normal Rat Osteoblast Cultures*

Endocrinology ◽  
1991 ◽  
Vol 128 (3) ◽  
pp. 1496-1504 ◽  
Author(s):  
THOMAS A. OWEN ◽  
MICHAEL S. ARONOW ◽  
LEESA M. BARONE ◽  
BRIAN BETTENCOURT ◽  
GARY S. STEIN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Bone Matrix ◽  
Bone Cell ◽  
Pleiotropic Effects ◽  
Cell Phenotype ◽  
Normal Rat ◽  
Rat Osteoblast

Gene expression at single cell resolution associated with development of the bone cell phenotype: Ultrastructural and in situ hybridization analysis

Bone ◽  
1993 ◽  
Vol 14 (3) ◽  
pp. 347-352 ◽  
Author(s):  
Shirwin M. Pockwinse ◽  
Jeanne B. Lawrence ◽  
Robert H. Singer ◽  
Janet L. Stein ◽  
Jane B. Lian ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Situ Hybridization ◽  
Single Cell ◽  
Bone Cell ◽  
Hybridization Analysis ◽  
Cell Phenotype

scholarly journals Concepts of Osteoblast Growth and Differentiation: Basis for Modulation of Bone Cell Development and Tissue Formation

1992 ◽  
Vol 3 (3) ◽  
pp. 269-305 ◽  
Author(s):  
Jane B. Lian ◽  
Gary S. Stein
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Three Dimensional ◽  
Bone Cell ◽  
Cell Phenotype ◽  
Specific Gene ◽  
Gene Promoters ◽  
Developmental Sequence ◽  
Combined Application ◽  
Bone Cell Differentiation

The combined application of molecular, biochemical, histochemical, and ultrastructural approaches has defined a temporal sequence of gene expression associated with development of the bone cell phenotype in primary osteoblast cultures. The peak levels of expressed genes reflect a developmental sequence of bone cell differentiation characterized by three principal periods: proliferation, extracellular matrix maturation and mineralization, and two restriction points to which the cells can progress but cannot pass without further signals. The regulation of cell growth and bone-specific gene expression has been examined during this developmental sequence and is discussed within the context of several unique concepts. These are (1) that oncogene expression in proliferating osteoblasts contributes to the suppression of genes expressed postproliferatively, (2) that hormone modulation of a gene is dependent upon the maturational state of the osteoblast, and (3) that chromatin structure and the presence of nucleosomes contribute to three-dimensional organization of gene promoters that support synergistic and/or antagonistic activities of physiologic mediators of bone cell growth and differentiation.

scholarly journals Constitutive expression of calreticulin in osteoblasts inhibits mineralization.

1995 ◽  
Vol 131 (5) ◽  
pp. 1351-1359 ◽  
Author(s):  
R St-Arnaud ◽  
J Prud'homme ◽  
C Leung-Hagesteijn ◽  
S Dedhar
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Cell Function ◽  
Constitutive Expression ◽  
Bone Cell ◽  
Nuclear Hormone Receptor ◽  
Expression Vectors ◽  
Transfected Cells

Recent studies have shown that the multifunctional protein calreticulin can localize to the cell nucleus and regulate gene transcription via its ability to bind a protein motif in the DNA-binding domain of nuclear hormone receptors. A number of known modulators of bone cell function, including vitamin D, act through this receptor family, suggesting that calreticulin may regulate their action in bone cells. We have used a gain-of-function strategy to examine this putative role of calreticulin in MC3T3-E1 osteoblastic cells. Purified calreticulin inhibited the binding of the vitamin D receptor to characterized vitamin D response elements in gel retardation assays. This inhibition was due to direct protein-protein interactions between the vitamin D receptor and calreticulin. Expression of calreticulin transcripts declined during MC3T3-E1 osteoblastic differentiation. MC3T3-E1 cells were transfected with calreticulin expression vectors; stably transfected cell lines overexpressing recombinant calreticulin were established and assayed for vitamin D-induced gene expression and the capacity to mineralize. Constitutive calreticulin expression inhibited basal and vitamin D-induced expression of the osteocalcin gene, whereas osteopontin gene expression was unaffected. This pattern mimicked the gene expression pattern observed in parental cells before down-regulation of endogenous calreticulin expression. In long-term cultures of parental or vector-transfected cells, 1 alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3) induced a two- to threefold stimulation of 45Ca accumulation into the matrix layer. Constitutive expression of calreticulin inhibited the 1,25(OH)2D3-induced 45Ca accumulation. This result correlated with the complete absence of mineralization nodules in long-term cultures of calreticulin-transfected cells. These data suggest that calreticulin can regulate bone cell function by interacting with specific nuclear hormone receptor-mediated pathways.

Rescue diet restores bone matrix mineralization in mice with a non-functioning vitamin D receptor

2019 ◽  
Author(s):  
Barbara Misof ◽  
Stephane Blouin ◽  
Markus Hartmann ◽  
Jochen Hofstaetter ◽  
Klaus Klaushofer ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Bone Matrix ◽  
Matrix Mineralization ◽  
Bone Matrix Mineralization

scholarly journals Role of glucuronidated 25-hydroxyvitamin D on colon gene expression in mice

2020 ◽  
Vol 319 (2) ◽  
pp. G253-G260
Author(s):  
Carmen J. Reynolds ◽  
Nicholas J. Koszewski ◽  
Ronald L. Horst ◽  
Donald C. Beitz ◽  
Jesse P. Goff
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

We found that 25OHD-Gluc, an endogenously produced metabolite, is delivered to the colon via bile to induce vitamin D-mediated responses in the colon.

scholarly journals A Hyaluronan and Platelet-Rich Plasma Hydrogel for Mesenchymal Stem Cell Delivery in the Intervertebral Disc: An Organ Culture Study

2021 ◽  
Vol 22 (6) ◽  
pp. 2963
Author(s):  
Fabrizio Russo ◽  
Luca Ambrosio ◽  
Marianna Peroglio ◽  
Wei Guo ◽  
Sebastian Wangler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intervertebral Disc ◽  
Organ Culture ◽  
Platelet Rich Plasma ◽  
Cell Activity ◽  
Human Mesenchymal Stem Cells ◽  
Cell Phenotype ◽  
Cytokeratin 19 ◽  
Stem Cell Delivery ◽  
Normal Metabolism

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 106 or 2 × 106 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 μL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.

scholarly journals THU0235 VITAMIN D AND INTERFERON SIGNATURE GENE EXPRESSION IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 344.3-345
Author(s):  
R. Magro ◽  
C. Saliba ◽  
L. Camilleri ◽  
C. Scerri ◽  
A. Borg
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Significant Negative Correlation ◽  
Systemic Lupus ◽  
Interferon Signature ◽  
Hydroxyvitamin D ◽  
Signature Genes ◽  
25 Hydroxyvitamin D

Background:Vitamin D deficiency is more prevalent in patients with systemic lupus eythematosus (SLE) as a result of sun avoidance.1The potential negative impact of vitamin D deficiency on SLE disease activity has been shown in a number of studies.2The expression of the interferon signature genes in SLE correlates positively with disease activity, and these genes are thought to mediate the clinical manifestations of the disease.3Objectives:The aim of this study was to establish whether a relationship exists between serum 25-hydroxyvitamin D level and the interferon signature gene expression in whole blood of SLE patients.Methods:Informed consent was obtained from 92 SLE patients who were over the age of 18 and who fulfilled the SLICC classification criteria for SLE. The patients were interviewed and blood samples were taken. SLE disease activity was measured by SLE disease activity index-2K (SLEDAI-2K). RNA extraction was performed from whole blood. QuantiGene Plex technology was used to measure the expression of 12 interferon signature genes in the extracted RNA. The study was approved by the University Research Ethics Committee.Results:92.4% of the cohort studied were female. 58.7% were receiving vitamin D3 supplementation at a mean dose of 1031IU daily. 27.2% had vitamin D insufficiency (25-hydroxyvitamin D 21-29ng/ml) and 15.2% were vitamin D deficient (25-hydroxyvitamin D <20ng/ml). Mean serum 25-hydroxyvitamin D was 30.75ng/ml (standard deviation 9.53 ng/ml). Median SLEDAI-2K was 4 (range 0-12). Serum 25-hydroxyvitamin D had a significant negative correlation with body mass index (BMI) (R=-0.258, p=0.006) but there was no significant negative correlation with SLEDAI-2K or with the expression of the interferon signature genes. The expression of most interferon signatures genes measured (IFI35, OAS1, MX1, IFITM1, STAT2, IFIT3, IFIT1, STAT1, SOCS1) had a significant positive correlation with SLEDAI-2K.Conclusion:This study did not show a significant relationship between serum vitamin D level and disease activity. In keeping with this, there was no significant negative correlation between serum 25-hydroxyvitamin D and interferon signature gene expression. Further prospective studies and randomised controlled trials are required to study this relationship in greater depth.References:[1]Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev. 2006; 5: 114-7.[2]Sahebari M, Nabavi N, Salehi M. Correlation between serum 25(OH)D values and lupus disease activity: an original article and a systematic review with meta-analysis focusing on serum VitD confounders.Lupus2014; 23: 1164-77.[3]Arasappan D, Tong W, Mummaneni P, Fang H, Amur S. Meta-analysis of microarray data using a pathway-based approach identifies a 37-gene expression signature for systemic lupus erythematosus in human peripheral blood mononuclear cells. BMC Med. 2011; 9: 65.Disclosure of Interests: :None declared

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