Schmid, Rainer and Bosserhoff, Anja-Katrin (2014) Redundancy in regulation of chondrogenesis in MIA/CD-RAP-deficient mice. MECHANISMS OF DEVELOPMENT, 131. pp. 24-34. ISSN 0925-4773, 1872-6356
Full text not available from this repository. (Request a copy)Abstract
Recent in vitro analysis of MIA/CD-RAP-deficient (MIA(-/-)) mesenchymal stem cells revealed altered chondrogenic differentiation, characterised by enhanced proliferation and delayed differentiation. However, adult MIA(-/-) mice develop normally and show only ultrastructural defects of the cartilage but no major abnormalities. We therefore focused, in this study, on chondrogenesis in vivo in MIA(-/-) mouse embryos to reveal potential molecular changes during embryogenesis and possible redundant mechanisms, which explain the almost normal phenotype despite MIA/CD-RAP loss. In situ hybridisation analysis revealed larger expression areas of Col2a1 and Sox9 positive, proliferating chondrocytes at day 15.5 and 16.5 of embryogenesis in MIA(-/-) mice. The initially diminished zone of Col10a1-expressing hypertrophic chondrocytes at day 15.5 was compensated at day 16.5 in MIA(-/-) embryos. Supported by in vitro studies using mesenchymal stem cells, we discovered that chondrogenesis in MIA(-/-) mice is modified by enhanced Sox9, Sox6 and AP-2a expression. Finally, we identified reduced AP1 and CRE activity, analysed by reporter gene- and electrophoretic mobility shift assays, important for redundancy mechanism which rescued delayed hypertrophic differentiation and allows normal development of MIA(-/-) mice. In summary, as observed in other knockout models of molecules important for cartilage development and differentiation, viability and functional integrity is reached by remarkable molecular redundancy in MIA/CD-RAP knockout mice. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HORMONE-RELATED PEPTIDE; CHONDROCYTE DIFFERENTIATION PATHWAY; MELANOMA INHIBITORY-ACTIVITY; II COLLAGEN GENE; TRANSCRIPTION FACTOR; BONE-FORMATION; X COLLAGEN; CBFA1-DEFICIENT MICE; TARGETED DISRUPTION; PTH/PTHRP RECEPTOR; Chondrogenesis; MIA/CD-RAP; Sox9; Differentiation; Cell signalling; MIA-knockout mouse |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Nov 2019 09:50 |
| Last Modified: | 28 Nov 2019 09:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10770 |
Actions (login required)
 |
View Item |
