ArticleAmerican journal of human genetics2016
Identification and Functional Characterization of RSPO2 as a Susceptibility Gene for Ossification of the Posterior Longitudinal Ligament of the Spine.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Pooled it
- Macrophage-driven pathological ossification of the posterior longitudinal ligament: mechanistic insights and therapeutic opportunities.Bone research · 2026Review
- Baseline characteristics, perioperative complications, and 1-year outcomes in cervical OPLL versus cervical spondylotic myelopathy: a multicenter retrospective cohort study.North American Spine Society journal · 2026Article
- [Radiological characteristics and associated factors of single-level cervical disc herniation combining with focal ossification of posterior longitudinal ligament].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Article
- Single-cell transcriptome profiling reveals the heterogeneity of ossification of the posterior longitudinal ligament (OPLL) and its immune microenvironment.Cell biology and toxicology · 2026Article
- Angiogenesis in ossification of the posterior longitudinal ligament: progress from mechanism to targeted intervention.Frontiers in cell and developmental biology · 2026Review
- Involvement of the Wnt/β-catenin signalling pathway in heterotopic ossification and ossification-related diseases.Journal of cellular and molecular medicine · 2024Review
- Patients with a large ossification of the posterior longitudinal ligament have a higher incidence of arteriosclerosis in the carotid artery.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2024Article
- A novel CCDC91 isoform associated with ossification of the posterior longitudinal ligament of the spine works as a non-coding RNA to regulate osteogenic genes.American journal of human genetics · 2023Article
- Review of Basic Research about Ossification of the Spinal Ligaments Focusing on Animal Models.Journal of clinical medicine · 2023Review
- Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 in osteoarthritis.Annals of the rheumatic diseases · 2023Article
- The biological functions and related signaling pathways of SPON2.Frontiers in oncology · 2023Review
- RSPO2 defines a distinct undifferentiated progenitor in the tendon/ligament and suppresses ectopic ossification.Science advances · 2022Article
- LGR5 regulates osteogenic differentiation of human thoracic ligamentum flavum cells by Wnt signalling pathway.Journal of cellular and molecular medicine · 2022Article
- Genetic Odyssey to Ossification of the Posterior Longitudinal Ligament in the Cervical Spine: A Systematic Review.Neurospine · 2022Article
- Small extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1.Nature communications · 2022Article
- Comparison of C2 dome-like laminectomy with C2 partial laminectomy for upper cervical ossification of the posterior longitudinal ligament.Frontiers in surgery · 2022Article
- Evidence for a genetic contribution to the ossification of spinal ligaments in Ossification of Posterior Longitudinal Ligament and Diffuse idiopathic skeletal hyperostosis: A narrative review.Frontiers in genetics · 2022Review
- Synergistic roles of Wnt modulators R-spondin2 and R-spondin3 in craniofacial morphogenesis and dental development.Scientific reports · 2021Article
- Association between ossification of the longitudinal ligament of the cervical spine and arteriosclerosis in the carotid artery.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common spinal disorder that results from ectopic ossification of the posterior longitudinal ligament and causes intractable myelopathy and radiculopathy. In a previous genome-wide association study (GWAS), we found six loci associated with OPLL; however, susceptibility genes in these loci have not been identified yet. Here, we examined one of the GWAS loci and identified RSPO2 (encoding R-spondin 2) as a susceptibility gene for OPLL. R-spondin 2 is a secreted agonist of canonical Wnt-β-catenin signaling. RSPO2 was decreased in the early stage of chondrocyte differentiation. R-spondin 2 inhibited expression of genes encoding early chondrocyte differentiation markers by activating Wnt-β-catenin signaling. rs374810, the most significantly associated SNP in the GWAS locus in chromosomal region 8q23.1 was located in the chondrocyte promoter region of RSPO2. A transcription factor, CCAAT-enhancer-binding protein β (C/EBPβ), specifically bound to the RSPO2 core promoter region containing rs374810 and increased RSPO2 expression. The risk allele of rs374810 affected the binding of the promoter with C/EBPβ and decreased the RSPO2 transcription in vitro and in vivo. Our genetic and functional data indicate that RSPO2 is a susceptibility gene for OPLL.
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