runx2 haploinsufficiency ameliorates the development of ossification of the posterior longitudinal ligamentrunx2 haploinsufficiency改善发展的后纵韧带骨化.pdfVIP

Runx2 Haploinsufficiency Ameliorates the Development of Ossification of the Posterior Longitudinal Ligament 1 1 2 1 1 2 Makiko Iwasaki , Jinying Piao , Ayako Kimura , Shingo Sato , Hiroyuki Inose , Hiroki Ochi , 1 1 1 3 Yoshinori Asou , Kenichi Shinomiya , Atsushi Okawa , Shu Takeda * 1 Department of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan, 2 Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan, 3 Section of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan Abstract 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