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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Systems Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1626337

This article is part of the Research TopicRecent Advancements in Musculoskeletal Regenerative MedicineView all 10 articles

Single-cell RNA-Seq reveals a repair pattern in cystic lesions in steroid induced osteonecrosis of the femoral head

Provisionally accepted
  • 1Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
  • 2National Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou, China
  • 3The fifth clinical college of Guangzhou university of Chinese medicine, Guangzhou, China
  • 4Guangzhou university of Chinese medicine, Guangzhou, China
  • 5Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, China
  • 6The Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
  • 7Bijie Traditional Chinese Medicine Hospital, Bijie, China

The final, formatted version of the article will be published soon.

Background: Studies have indicated that cystic lesions play a crucial role in the repair processes of steroid-induced osteonecrosis of the femoral head and its subsequent collapse. Here, we employed single-cell RNA sequencing (scRNA-seq) technology to investigate the transcriptomic landscape and repair mechanisms of cystic lesions in SIONFH. Methods: We applied scRNA-seq combined with computational approaches to characterize distinct cell subsets and their molecular signatures within cystic lesions from three SIONFH patients. Additionally, histological assays were conducted to observe pathological manifestations of these lesions. Results: Eight cell types were identified in cystic lesions of SIONFH. Among them, chondrocytes were divided into five subgroups. Among them, chondrocytes were divided into five subgroups: homeostatic chondrocytes (HomC), fibrocartilage chondrocytes (FC), prehypertrophic chondrocytes (preHTC), inflammatory chondrocytes (InflamC), and hypertrophic chondrocytes (HTC). Additionally, histological assays showed the presence of chondrocytes and a transition zone from chondrocytes to bone tissue within the cystic lesions. Notably, we report that one of the HTC clusters with CLIC3+ expression exhibited a strong involved in bone mineralization, osteoblast differentiation, and cell differentiation. Conclusion: We have delineated the cellular heterogeneity and molecular signatures of cystic lesions in SIONFH. The results reveal a distinct repair program within these lesions, which might be driven by chondrocyte hypertrophy and might culminate in osteogenic differentiation.

Keywords: Steroid-induced osteonecrosis of the femoral head, single-cell RNA sequencing, chondrocyte, cystic lesions, Osteogenic differentiation

Received: 12 May 2025; Accepted: 04 Aug 2025.

Copyright: © 2025 Peng, Tian, Lin, Fang, Yao, Yang, Hou, Xiao, Lu, He, He, Xiao and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Huan Xiao, Bijie Traditional Chinese Medicine Hospital, Bijie, China
Qiu-Shi Wei, National Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou, China

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