title: Runx2 haploinsufficiency ameliorates the development of ossification of the posterior longitudinal ligament.
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 ENPP1(ttw/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 ENPP1(ttw/ttw) mice. Runx2 haploinsufficiency ameliorated the development of ectopic calcification in the ENPP1(ttw/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.
authors.affiliation: Department of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Jinying
authors.initials: J
authors.lastname: Piao
authors.forename: Ayako
authors.initials: A
authors.lastname: Kimura
authors.forename: Shingo
authors.initials: S
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inose
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ochi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Asou
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okawa
authors.forename: Shu
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D057895:Haploinsufficiency; D051379:Mice; D017887:Ossification of Posterior Longitudinal Ligament / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit