Redundancy in regulation of chondrogenesis in MIA/CD-RAP-deficient mice
Schmid R, Bosserhoff AK (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Book Volume: 131
Pages Range: 24-34
Journal Issue: 1
DOI: 10.1016/j.mod.2013.11.001
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-2α 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. © 2013 Elsevier Ireland Ltd.
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Germany (DE)How to cite
APA:
Schmid, R., & Bosserhoff, A.K. (2014). Redundancy in regulation of chondrogenesis in MIA/CD-RAP-deficient mice. Mechanisms of Development, 131(1), 24-34. https://dx.doi.org/10.1016/j.mod.2013.11.001
MLA:
Schmid, Rainer, and Anja Katrin Bosserhoff. "Redundancy in regulation of chondrogenesis in MIA/CD-RAP-deficient mice." Mechanisms of Development 131.1 (2014): 24-34.
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