Exosome-mediated cholesterol flow drives scoliosis progression via promoting the spinal cartilage-bone positive feedback

  • Commun Biol. 2026 Apr 3;9(1):547. doi: 10.1038/s42003-026-09960-w.
Min Zuo  #  1 ,  Haixia Xu  #  1 ,  Yuying Yang  #  1 ,  Wenbo Wang  1 ,  Jianghong Zhou  1 ,  Guojun Li  1 ,  Jing Zhao  1 ,  Rangru Liu  2 ,  Huanxiong Chen  3 ,  Hua Wang  4
Affiliations
  • 1. NHC Key Laboratory of Tropical Disease Control, School of Life Sciences and Medical Technology, Department of Spine Surgery, Hainan Province Clinical Medical Center, The First Affiliated Hospital, Hainan Medical University, Haikou, 571199, Hainan, China.
  • 2. Hainan Provincial Key Laboratory of Research and Development on Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou, 571199, Hainan, China. [email protected].
  • 3. Department of Spine Surgery, Hainan Province Clinical Medical Center, The Second Affiliated Hospital of Hainan Medical University, Haikou, 571199, Hainan, China. [email protected].
  • 4. NHC Key Laboratory of Tropical Disease Control, School of Life Sciences and Medical Technology, Department of Spine Surgery, Hainan Province Clinical Medical Center, The First Affiliated Hospital, Hainan Medical University, Haikou, 571199, Hainan, China. [email protected].
  • # Contributed equally.
PMID: 41933055 DOI: 10.1038/s42003-026-09960-w
Abstract

Adolescent Idiopathic Scoliosis (AIS) is the most common form of spinal deformity among adolescents. To explore its etiology of progression and scoliosis-modifying drugs, chondrocytic senescence was confirmed in AIS facet joint cartilage by analyzing clinical specimen. Furthermore, through 4D/480 label-free proteomics analysis, we identified an exosome-mediated positive feedback loop during scoliosis progression, which driving the elevation of Cholesterol flow between spinal cartilage and vertebra. To further investigate the pathological significance of the loop in vivo, high-cholesterol flow was reconstructed in C57BL/6 J mice by injecting with recombinant adeno-associated virus rAAV9-Runx2-HMGCR. Our results confirmed the important role of the positive feedback loop in the development of scoliosis. Meanwhile, Avasimibe or/and Corylin were used to delay the scoliosis progression by targeting the key exosomal proteins apoB (Apolipoprotein B-100) or/and HSP90β (Heat Shock Protein 90-beta). This research extends the etiology of scoliosis progression and provides an alternative perspective for scoliosis non-surgical treatment.

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