Research ArticleOssification of the posterior ligament is mediated by osterix via inhibition of the β-catenin signaling pathway

- Osx was upregulated in human OPLL tissue.
- Osx mediated ossification of posterior ligament.
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- Wnt/β-catenin signaling was involved in Osx mediated ossification of posterior ligament.
- Osx regulated Wnt/β-catenin signaling via DKK1.

Ossification of the posterior longitudinal ligament (OPLL) involves ectopic calcification of the spinal ligament preferentially at the cervical spine. OPLL is associated with different diseases and occurs by endochondral ossification, which is associated with the activity of different transcription factors. However, the pathogenesis of OPLL remains unclear. Here, we investigated the role of osterix (Osx), a transcription factor that functions downstream of Runx2 and is an important regulator of osteogenesis, in the process of OPLL in a dexamethasone (Dex)-induced model of spinal ligament ossification. Our results showed that Osx is upregulated in patients with OPLL and during the ossification of ligament cells in parallel with the upregulation of osteogenic markers including osteocalcin (OCN), alkaline phosphatase (ALP) and collagen-1 (Col-1). Dex-induced ossification of ligament cells was associated with the downregulation and inactivation of β-catenin, and these effects were offset by Osx knockdown. Activation of β-catenin signaling abolished the effect of Dex on ossification and the upregulation of osteogenic markers. Taken together, our results suggest that OPLL is mediated by Osx via a mechanism involving the Wnt/β-catenin signaling pathway, providing a basis for further research to identify potential targets for the treatment of OPLL.