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Gene expression in normotopic and heterotopic human bone: increased level of SP7 mRNA in pathological tissue

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Abstract

Head injury-induced heterotopic ossification (HO) develops at vicinity of joints and in severe cases requires surgical intervention. Our previous study demonstrated high mRNA levels of osteocalcin (OC), type 1 collagen (COL1), osteonectin and RUNX2/CBFA1 in osteocytes and lining osteoblasts from non-evolutive HO compared to equivalent healthy cells from the proximal femoral shaft of patients receiving prosthesis. This allowed a first molecular characterisation of this pathological bone. The aims of this study is to extend the analysis to 10 more genes and determine those involved in the high OC mRNA level observed in pathological bone samples. RNAs were prepared from normotopic and heterotopic human bone samples digested by collagenase. After cDNA synthesis, mRNA levels were determined by real-time PCR and normalised using β actin and glyceraldehyde-3-phosphate dehydrogenase. OSTERIX/SP7 expression was observed for the first time in human adult bone biopsies. In HO samples higher levels of SP7 (four- to sevenfold increase) and 1α,25-dihydroxy vitamin D3 receptor (VDR) (two- to threefold increase) were observed compared to control samples. Moreover, SP7 level was correlated to OC and RUNX2 levels. In control samples, OC and SP7 levels were correlated. Our study further confirms that the involvement of SP7 in bone physiology is not only limited to the developmental step. Moreover, our results support the hypothesis that in HO the high level of OC expression could be due not only to an increase in RUNX2, but also in SP7 or VDR or to an imbalance in their respective activities.

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Abbreviations

(1,25(OH)2D3):

1α,25-Dihydroxyvitamin D3

AP-1:

Activator protein-1

COL1:

Type 1 collagen

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GR:

Glucocorticoid receptor

GRE:

Glucocorticoid response element

HO:

Heterotopic ossification

OC:

Osteocalcin

RT-PCR:

Reverse transcriptase-polymerase chain reaction

RXR:

Retinoid X receptor

SP7:

Specificity protein 7

VDR:

1α,25-Dihydroxyvitamin D3 receptor

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Acknowledgements

The authors thank Dr. B. Bouxin for work expertise and assistance, Dr. D. Lamy for statistical analysis and B. Christmas for critical reading of the manuscript. This work was supported in part by grants from the Société Francaise de Rhumatologie (SFR) and by the Contrat Plan Etat Région Nord-Pas de Calais.

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Authors and Affiliations

  1. LR2B—Laboratoire de Recherche sur les Biomatériaux et les Biotechnologies, Université du Littoral Côte d’Opale, Quai Masset, Bassin Napoléon, BP 120, 62327, Boulogne-sur-Mer, France

    C. Chauveau, O. Broux, P. Hardouin, J. Jeanfils & J. C. Devedjian

  2. Institut Calot, Groupe Hopale, Berck-sur-Mer, France

    C. Delecourt

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  1. C. Chauveau
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  2. O. Broux
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  3. C. Delecourt
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  4. P. Hardouin
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  5. J. Jeanfils
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  6. J. C. Devedjian
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Correspondence to J. C. Devedjian.

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C. Chauveau and O. Broux contributed equally to this work.

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Chauveau, C., Broux, O., Delecourt, C. et al. Gene expression in normotopic and heterotopic human bone: increased level of SP7 mRNA in pathological tissue. Mol Cell Biochem 318, 81–87 (2008). https://doi.org/10.1007/s11010-008-9859-5

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  • DOI: https://doi.org/10.1007/s11010-008-9859-5

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