Establishment and characterization of new osteoclast progenitor cell lines derived from osteopetrotic and wild type mice.
Malignant infantile osteopetrosis is a rare and lethal disease characterized by the absence of bone resorption due to inactive osteoclasts (OCLs). Among the murine models of osteopetrosis, the Tcirg1oc/oc mouse is the most resembling to the human pathology. In the majority of patients as in Tcirg1oc/oc mouse, the gene involved is the Tcirg1 gene, encoding the a3 subunit of the vacuolar proton pump. However, to date, no osteoclastic cell lines from osteopetrotic mice are available to facilitate the study of either OCL differentiation in osteopetrosis or the factors involved in the control of Tcirg1 gene expression. Heterozygotes Tcirg1+/oc mice were crossed with p53+/- mice to obtain homozygotes p53-/-Tcirg1oc/oc and p53-/-Tcirg1+/+ animals. The p53-/-Tcirg1oc/oc mice display the same bone and hematological phenotype as the original Tcirg1oc/oc mice. From the bone marrow of these mice, we have derived cell lines named POC-MGoc/oc and POC-MG+/+. These cell lines express standard osteoclastogenic markers and differentiate into OCLs in the presence of RANK-L and M-CSF. Furthermore, both cell lines can be transduced by a lentiviral vector with a high efficiency and without alteration of their OCL differentiation potential. Therefore, these cell lines provide valuable new tools to study the differentiation and function of osteoclasts in normal and resorption defective conditions.
Blin-Wakkach
Claudine
C
CNRS/UNSA Unité K2943, IFR50, Faculté de Médecine, and Service de Rhumatologie, Hôpital L'Archet 1, Nice, France.
Breuil
Véronique
V
Quincey
Danielle
D
Bagnis
Claude
C
Carle
Georges F
GF
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002352:Carrier Proteins / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003433:Crosses, Genetic; D005269:Femur / Q000166:cytology; D005822:Genetic Vectors; D006579:Heterozygote; D006720:Homozygote; D016086:Lentivirus / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology; D010022:Osteopetrosis / Q000235:genetics* / Q000473:pathology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014162:Transfection
D015415:Biomarkers; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor