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Aptamer-functionalized apoptotic vesicles ameliorate osteoarthritis via resuming mitochondria OXPHOS of chondrocytes

Zeying Wang1, Yuhe Jiang1, Xiuyun Xu1

  • 1Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, National Clinical Research Center for Oral Disease, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 P. R. China.

Science Advances
|June 17, 2026
PubMed

Insights

This study developed aptamer-functionalized apoptotic vesicles (tgg2@apoVs) for osteoarthritis treatment. The novel system targets chondrocytes, enhances mitochondrial function, and alleviates OA symptoms, offering a promising therapeutic strategy.

Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Mitochondrial Biology

Background:

  • Osteoarthritis (OA) progression is linked to chondrocyte mitochondrial dysfunction and cartilage matrix imbalance.
  • Mesenchymal stem cell-derived apoptotic vesicles (apoVs) show therapeutic potential but lack chondrocyte targeting and joint retention.
  • Aptamer tgg2 specifically binds to chondrocytes, offering a potential targeting strategy.

Purpose of the Study:

  • To functionalize apoVs with tgg2 for enhanced chondrocyte targeting and develop a sustained-release system for OA treatment.
  • To investigate the therapeutic efficacy of tgg2@apoVs in vitro and in vivo.
  • To elucidate the molecular mechanism of apoVs in improving chondrocyte mitochondrial energy metabolism.

Main Methods:

  • Functionalization of apoVs with tgg2 via Schiff base reaction.
  • Fabrication of an injectable hyaluronic acid methacryloyl (HAMA) hydrogel sustained-release system.
  • In vitro assessment of chondrocyte extracellular matrix synthesis and mitochondrial oxidative phosphorylation (OXPHOS).
  • In vivo evaluation of OA symptom alleviation in a mouse model.

Main Results:

  • tgg2@apoVs demonstrated high conjugation efficiency and significantly promoted chondrocyte extracellular matrix synthesis and mitochondrial OXPHOS in vitro.
  • The HAMA hydrogel system loaded with tgg2@apoVs effectively alleviated OA symptoms in vivo.
  • ApoVs were found to activate transcription factor Yin Yang 1 (YY1), up-regulating Cox7c expression and enhancing mitochondrial OXPHOS.

Conclusions:

  • The tgg2@apoVs sustained-release system offers a viable and cost-effective approach for osteoarthritis treatment.
  • The identified molecular mechanism provides insights into apoVs' role in chondrocyte mitochondrial energy metabolism.
  • This approach holds potential for broader applications in treating energy metabolism-related diseases.

Related Concept Videos

Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.