Oxytocin-loaded hydrogel promotes cartilage regeneration and regulates microenvironment.

Tianming Wang, Xiao Zhao, Jiayi Li, Chongchong Yin, Bo Jiang, Jiaming Xie, Binghao Wang, Yufeng Wang, Zhicheng Cao, Qingqiang Yao, Shengnai Zheng, Jisheng Sui, Kun Zhu
Author Information
  1. Tianming Wang: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China. ORCID
  2. Xiao Zhao: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China. ORCID
  3. Jiayi Li: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China.
  4. Chongchong Yin: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China.
  5. Bo Jiang: Children's Hospital of Nanjing Medical University, Nanjing 210000, People's Republic of China.
  6. Jiaming Xie: Children's Hospital of Nanjing Medical University, Nanjing 210000, People's Republic of China.
  7. Binghao Wang: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China.
  8. Yufeng Wang: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China.
  9. Zhicheng Cao: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China.
  10. Qingqiang Yao: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China.
  11. Shengnai Zheng: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China.
  12. Jisheng Sui: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China.
  13. Kun Zhu: Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, People's Republic of China. ORCID

Abstract

Osteoarthritis is a common orthopedic condition, and traditional treatment methods often fail to regenerate cartilage effectively. Oxytocin (OXT) is a neuropeptide that plays a crucial role in the skeletal system. Hyaluronic acid (HAMA) hydrogel has emerged as a key carrier for cartilage repair due to its excellent biocompatibility and biodegradability. Combining OXT with HAMA hydrogel and implanting it at the site of cartilage defects can effectively promote cartilage regeneration. Cartilage damage often results in an altered microenvironment, characterized by macrophage polarization and high levels of reactive oxygen species (ROS). Oxidative stress can stimulate macrophages to produce more pro-inflammatory factors. OXT can inhibit the secretion of pro-inflammatory cytokines such as TNF-, IL-6, and IL-1by interacting with the STAT3/NF-B signaling pathway, as well as the PI3K/Akt and mitogen-activated protein kinase pathways, thereby inducing the polarization of macrophages from the M1 phenotype to the M2 phenotype and alleviating the inflammatory response. OXT can also enhance the expression of NRF and HO-1, which helps eliminate ROS and suppress the expression of pro-inflammatory factors. Regulating the microenvironment of cartilage damage is beneficial for cartilage protection and repair. OXT activates the CFOS/AP-1 and STAT1/JAK2 pathways, which together act on MMP2 and MMP9 to alleviate cartilage degeneration. The STAT1/JAK2 pathway can further increase the expression of Col2, thereby protecting chondrocytes. Additionally, OXT can directly boost the protein levels of SOX9 and COMP, promoting chondrocyte proliferation and cartilage protection, ultimately achieving the therapeutic goal for arthritis. This study explores the potential of HAMA hydrogel as a delivery system for OXT and analyzes their impact on cartilage regeneration and anti-inflammatory properties. This research provides a novel strategy for the treatment of cartilage injuries.

Keywords

MeSH Term

Hydrogels
Animals
Oxytocin
Regeneration
Cellular Microenvironment
Cartilage
Hyaluronic Acid
Mice
Macrophages
Chondrocytes
Chondrogenesis

Chemicals

Hydrogels
Oxytocin
Hyaluronic Acid

Word Cloud

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