Ossification of the posterior ligament is mediated by osterix via inhibition of the β-catenin signaling pathway.
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.
Department of Orthopedics, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai 200003, China.
Lei
L
Shi
Department of Orthopedics, Affiliated Hospital of Taishan Medical University, 706 Taishan Street, Tai'an 271000, Shangdong Province, China.
Guodong
G
Cai
Department of Orthopedics, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai 200003, China.
Jiangang
J
Shi
Department of Orthopedics, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai 200003, China.
Yongfei
Y
Guo
Department of Orthopedics, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai 200003, China.
Dechun
D
Chen
Department of Orthopedics, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai 200003, China.
Deyu
D
Chen
Department of Orthopedics, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai 200003, China. Electronic address: hsyangcz@126.com.
Haisong
H
Yang
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D017846:Longitudinal Ligaments / Q000378:metabolism / Q000473:pathology; D017887:Ossification of Posterior Longitudinal Ligament / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D003907:Dexamethasone; D018021:Lithium Chloride
Dexamethasone; Ossification of the posterior longitudinal ligament; Osterix; β-catenin signaling pathway