Identification of genes regulated during osteoblastic differentiation by genome-wide expression analysis of mouse calvaria primary osteoblasts in vitro

Roman-Roman, Sergio; García, Teresa; Jackson, Amanda; Theilhaber, Joachim; Rawadi, Georges; Connolly, Timothy M.; Spinella-Jaegle, Sylviane; Kawai, Shinji; Courtois, B; Bushnell, Steven; Auberval, Marielle; Call, Kathy; Baron, Roland

doi:10.1016/s8756-3282(03)00052-8

Cited by 65 publications

(47 citation statements)

References 45 publications

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“…We observed reduced expression of CCN1, but not CCN2, during osteoblast differentiation, suggesting a specific role of CCN1 in maintenance of the mesenchymal stem cell phenotype. Similarly, gene expression patterns during osteoblast differentiation in cultures from calvaria have shown that the three CCN genes were differentially expressed, CCN1 and CCN2 expression being strongly repressed (33). Importantly, in contrast to CCN1, we were unable to detect CCN3 expression in human mesenchymal stem cells during any phase of their differentiation toward terminal osteoblasts.…”

Section: Discussioncontrasting

confidence: 62%

Prognostic Value of CCN3 in Osteosarcoma

Perbal

Zuntini²,

Zambelli³

et al. 2008

Clinical Cancer Research

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Purpose: Osteosarcoma, the most common bone tumor, lacks prognostic markers that could distinguish patients before therapy and drive treatment choices.We assessed the prognostic value of CCN1, CCN2, and CCN3 genes, involved in fundamental biological processes. Experimental Design: Expression of CCN1, CCN2, and CCN3 was measured by quantitative PCR in 45 newly diagnosed osteosarcomas. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations with osteoblastic differentiation and/or drug response genes were assessed in tumor cells using Spearman correlation and Fisher's exact tests. Results: CCN1 and CCN2 expression was associated with genes involved in commitment of mesenchymal stem cells toward osteoblasts and in early phases of osteoblastic differentiation (RUNX family genes; cadherin 4, 11, and 13; jun and fos; collagen I and SPARC). Although CCN3 is barely expressed in normal proliferating osteoblasts and mesenchymal stem cells, its expression was generally high in osteosarcoma and its level of expression did not correlate with any specific osteoblastic differentiation genes. High expression of CCN3 significantly correlated with worse prognosis in osteosarcoma. This may be only partly explained by the association with the expression of multidrug resistance^related protein 1and 4, two ATP-binding cassette transporters that also acted as predictors of worse outcome in our study. Conclusions: Our study showed temporal and coordinated expression of CCN1, CCN2, and CCN3 genes during osteoblastic differentiation and highlighted significant differences between human normal and osteosarcoma cell differentiation in vitro. CCN1 and CCN2 expression shows no prognostic relevance in osteosarcoma. In contrast, assessment for CCN3 expression levels at diagnosis may represent a useful molecular tool to early identification of patients with different prognosis.Osteosarcomas constitute a heterogeneous group of malignant neoplasms, the great majority of which are represented by high-grade tumors with advanced phenotypes at the time of diagnosis. In spite of their relatively low incidence, <10% of all tumors, these sarcomas represent a considerable burden because they are one of the most frequent pediatric bone tumors and remain prominent among both teenagers and young adults.Although new therapies that combine high-dose chemotherapy with local control of the tumor have led to a significant benefit in terms of patient survival (1, 2), there is a need for molecular prognostic markers that would permit, at the time of diagnosis, identification of poorly responsive tumors that may benefit from modified treatment regimen.To date, aside from metastasis at presentation, the other most accepted prognostic factors are based on the response to treatment (percentage of necrosis or P-glycoprotein expression). However, P-glycoprotein overexpression still suffers from an undisputed recognition as a prognostic factor (2 -4) and of lack of suitable drugs that are available for clinical practice, impairing its ...

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Section: Discussioncontrasting

confidence: 62%

Prognostic Value of CCN3 in Osteosarcoma

Perbal

Zuntini²,

Zambelli³

et al. 2008

Clinical Cancer Research

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“…Many independent studies of gene expression patterns during osteoblast differentiation have been described (10,33,44,45), in which apoE was the only apolipoprotein strongly induced during this process (10,33). ApoE regulated bone metabolism in mice is possible due to uptake of lipid and lipid soluble vitamins such as vitamin K into osteoblasts (10).…”

Section: Discussionmentioning

confidence: 99%

“…The results showed that among the LDLR family, megalin was up-regulated, while LRP1 and the LDLR were down-regulated (33). However, the previous report only screened very few members of the LDLR family during osteoblastic differentiation.…”

Section: Introductionmentioning

confidence: 88%

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

Gui

Duan

Tang

et al. 2016

BST

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“…We further identified SXR-dependent vitamin K-responsive genes by microarray analysis using human osteoblastic cell line, MG63 cells stably overexpressing SXR [26]. The identified genes included Tsukushi which encodes a protein that has a collagen-accumulating effect [27], Matrilin2 which encodes a protein comprising extracellular matrix like collagen [28], and Cd14 which regulates osteoblastogenesis [29] and osteoclastogenesis by inducing differentiation of B cells [30,31]. These genes are induced even in the presence of warfarin, indicating their induction is independent of GGCX activity.…”

Section: Sxr-mediated Vitamin K Functions On Bone and Cartilagementioning

confidence: 99%

Vitamin K, SXR, and GGCX

Azuma¹,

Inoue²

2017

Vitamin K2 - Vital for Health and Wellbeing

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Vitamin K was discovered in 1929 as a substance essential for blood coagulation and had been clinically utilized before the precise mechanism of action became aware in 1970s. The function as a cofactor of γ-glutamyl carboxylase (GGCX) was the mechanism firstly discovered with the identification of several substrate proteins including blood coagulation factors and osteocalcin. Recently, we and others have shown that vitamin K has other modes of function, such as ligand of nuclear receptor SXR (steroid and xenobiotic receptor) and its murine ortholog PXR (pregnane X receptor) and modulator of protein kinase A (PKA) activity. Besides its importance in blood coagulation, involvement of vitamin K has been shown in two major aging-related diseases, osteoporosis and osteoarthritis. Based on clinical and epidemiological studies, vitamin K is shown to have protective roles for both of them. Interestingly, clinical studies concerning single nucleotide polymorphisms (SNPs) of GGCX and γ-carboxylated status of osteocalcin suggested relationship between GGCX activity and bone-protective effect, while recent findings from basic research indicated that vitamin K functions mediated by SXR/PXR as well as GGCX are important in the bone metabolism. We also suggested that cartilage-protective effect is mediated by SXR/PXR signaling by animal experiments using Pxr knockout mice.

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Identification of genes regulated during osteoblastic differentiation by genome-wide expression analysis of mouse calvaria primary osteoblasts in vitro

Cited by 65 publications

References 45 publications

Prognostic Value of CCN3 in Osteosarcoma

Prognostic Value of CCN3 in Osteosarcoma

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

Vitamin K, SXR, and GGCX

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