ArticleCell biology and toxicology2026
Single-cell transcriptome profiling reveals the heterogeneity of ossification of the posterior longitudinal ligament (OPLL) and its immune microenvironment.
Article in Cell biology and toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOssification of the posterior longitudinal ligament (OPLL) is a heterotopic ossification process of the posterior longitudinal ligament (PLL) that can compress the spinal cord and nerve roots, yet its cellular heterogeneity and pathogenesis remain unclear.
methodsWe performed single-cell RNA sequencing (scRNA-seq) with integrative computational analyses and histological validation on 4,683 cells from surgically resected cervical OPLL lesions obtained from human patients.
resultsWe identified 15 major cell subsets, including chondrocyte-lineage populations-progenitor/proliferative fibrocartilage chondrocytes (ProFCs), pre-hypertrophic chondrocytes (preHTCs), and hypertrophic chondrocytes (HTCs)-as well as osteoblasts, endothelial cells, and diverse immune cells. Pseudotime analysis suggested an inferred trajectory from cartilage progenitor-like cells through inflammatory/reactive and hypertrophic states toward osteogenic programs, with progressive activation of ossification, extracellular-matrix, and inflammation-related pathways. Cell-cell communication analyses showed coordinated immune-stromal crosstalk, with FGF signaling enriched in earlier pseudotime states and SPP1-CD44 signaling enriched in later states. SPP1 signals originated predominantly from HTCs, whereas macrophages were prominently involved in the broader inflammatory niche and immune-stromal communication within OPLL lesions. Consistently, SPP1/CD44-positive cells were enriched in OPLL tissues and further increased by IL-1β stimulation in vitro and in an Enpp1-driven OPLL mouse model.
conclusionsThis exploratory single-cell atlas suggests that an inflammatory niche may couple chondrocyte hypertrophy with osteogenic activation and highlights candidate immune-stromal pathways for future biomarker and therapeutic exploration in OPLL.
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