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 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.

Soft tissue ossification and condylar cartilage degeneration following TMJ disc perforation in a rabbit pilot study

“…6g). We examined the expression of runx2 by real time PCR, given runx2 is an early bone marker that is upregulated in heterotopic ossification of other soft tissues (15,26). Compared to TMJ disc cells in basal media, runx2 upregulated by 13.5 fold in TMJ disc cells in osteogenic media (Fig.…”

Role of Runx2 polymorphisms in risk and prognosis of ossification of posterior longitudinal ligament

“…32 Based on the understanding about the significance of Runx2 in normal formation of osteoblasts, investigations related to osteoblastrelevant disorders (e.g., OPLL) demonstrated that haploinsufficiency of Runx2 could impede development of OPLL in ENPP1 ttw/ttw mice, implying that normal Runx2 expressions may be essential to trigger OPLL. 33 In addition, research findings of Kishiya and his colleagues indicated that Runx2 might play a regulatory role in ectopic calcification through regulation of a downstream effector (i.e., angiopoietin-1), giving a hint that Runx2 could act as a critical regulator for the development and progression of OPLL. 7 However, previous researches were still insufficient to explain how Runx2 is linked with OPLL through its physiological and pathological roles.…”

Masticatory muscle tendon‐aponeurosis hyperplasia exhibits heterotopic calcification in tendons

“…On the other hand, heterotopic calcification of ligaments and tendons is associated with diseases such as ossification of the posterior longitudinal ligament (OPLL) and calcific tendinopathy (CTP). Runt‐related transcription factor 2 (Runx2) is expressed in OPLL‐like regions, and its elevation is a prerequisite for developing a complete OPLL‐like phenotype (Iwasaki et al , ). Heterotopic calcification in CTP is associated with collagenase‐induced degenerative tendon (Lui et al , ).…”