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Biochemistry - Physiology - Surgery

Runx2 Haploinsufficiency Ameliorates the Development of Ossification of the Posterior Longitudinal Ligament
Published: Tuesday, August 21, 2012
Author: Makiko Iwasaki et al.

by Makiko Iwasaki, Jinying Piao, Ayako Kimura, Shingo Sato, Hiroyuki Inose, Hiroki Ochi, Yoshinori Asou, Kenichi Shinomiya, Atsushi Okawa, Shu Takeda

Ossification of the Posterior Longitudinal Ligament (OPLL) is a disease that is characterized by the ectopic calcification of the ligament; however, the pathogenesis of OPLL remains to be investigated. We attempted to identify the in vivo role of Runx2, a master regulator of osteoblast differentiation and skeletal mineralization, in the pathogenesis of OPLL. The expression of Runx2 in the ligament was examined using in situ hybridization and immunohistochemistry and by monitoring the activity of a LacZ gene that was inserted into the Runx2 gene locus. To investigate the functional role of Runx2, we studied ENPP1ttw/ttw mice, a mouse model of OPLL, that were crossed with heterozygous Runx2 mice to decrease the expression of Runx2, and we performed histological and quantitative radiological analyses using 3D-micro CT. Runx2 was expressed in the ligament of wild-type mice. The induction of Runx2 expression preceded the development of ectopic calcification in the OPLL-like region of the ENPP1ttw/ttw mice. Runx2 haploinsufficiency ameliorated the development of ectopic calcification in the ENPP1ttw/ttw mice. Collectively, this study demonstrated that Runx2 is expressed in an OPLL-like region, and its elevation is a prerequisite for developing the complete OPLL-like phenotype in a mouse model of OPLL.