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Single-cell RNA-sequencing analysis reveals cellular states and intercellular communication of human lumbar facet-joint degeneration
Xiang-Yuan Chen, Wen Luo, Yue-Ying Zhang, Hui-Ying Li, Ping Wang, Dan-Dan Wang, College of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China
Xiang-Yuan Chen, Yuan-Zhen Chen, Dan-Dan Wang, Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Jinan 250062, Shandong Province, China
Yuan-Zhen Chen, Department of Pain Management, The Second Affiliated Hospital of Shandong First Medical University, Tai’an 271000, Shandong Province, China
Lei Wang, Department of Orthopaedics, The 960th Hospital of The People’s Liberation Army Joint Logistics Support Force, Jinan 250031, Shandong Province, China
Zhen-Tao Man, Wei Li, Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Co-first authors: Xiang-Yuan Chen and Wen Luo.
Co-corresponding authors: Dan-Dan Wang and Wei Li.
Author contributions: Chen XY and Luo W have played important and indispensable roles in the experimental design as co-first authors; Chen XY, Luo W, Chen YZ and Wang L performed the experiment; Chen XY, Zhang YY, Wang P, and Wang DD analyzed the data; Chen YZ, Wang L and Li HY collected samples and analyzed clinical data; Li W and Wang DD have played important and indispensable roles in the manuscript preparation as co-corresponding authors; Man ZT, Li W and Wang DD designed the research and revised the manuscript; Chen XY, Luo W, and Wang DD wrote the paper.
AI contribution statement: During the preparation of this manuscript, AI-assisted tools were used solely for language refinement and grammar correction to improve the clarity and readability of the text. No AI tools were used for any other aspect of this research.
Supported by the National Key R&D Program of China, No. 2022YFF0713100; and the Natural Science Foundation of Shandong Province, No. ZR2026MS1334.
Institutional review board statement: This study involving human participants was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Shandong First Medical University and Shandong Academy of Medical Sciences (No. R202204290099). Informed consent was received from all study participants.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Data sharing statement: Raw single-cell RNA sequencing data of all samples were uploaded to the Genome Sequence Archive (GSA) of the National Genomics Data Center (PRJCA016822), which are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human/s/E2WBojr6.
Corresponding author: Dan-Dan Wang, Additional Professor, College of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 6699 Qingdao Road, Huaiyin District, Jinan 250117, Shandong Province, China.
Received: July 6, 2026
Revised: August 20, 2026
Accepted: October 30, 2026
Published online: November 18, 2026
Processing time: 127 Days and 12.6 Hours
Revised: August 20, 2026
Accepted: October 30, 2026
Published online: November 18, 2026
Processing time: 127 Days and 12.6 Hours
Core Tip
Core Tip: This study provides a single-cell transcriptomic landscape of human lumbar facet joint (LFJ) cartilage degeneration across different degeneration stages. We identified stage-specific changes in chondrocyte and macrophage subpopulations and characterized their potential interactions during disease progression. Notably, proinflammatory chondrocytes were enriched in mild degenerated LFJs, whereas distinct macrophage populations emerged with advanced degeneration. Cell-cell communication analysis further revealed enhanced chondrocyte-macrophage crosstalk during degeneration. These findings provide new insights into the cellular heterogeneity and potential intercellular mechanisms underlying LFJ degeneration.