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Updated: Aug 5, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
PDGF-BB inhibits SP1/Angptl7 mediated chondro-endothelial crosstalk via stress-sensitivity Piezo1 regulation in
Zhengchao Wang1,2,3,4, Jiangxia Cheng2,3,4,5, Hongmei Li6
1Department of Sports Medicine, Wuhan Fourth Hospital, Wuhan, China.
Introduction:
Osteoarthritis (OA) involves cartilage degradation and subchondral bone alterations, yet the mechanisms of chondro-endothelial crosstalk remain unclear. Stress-sensitive Piezo1 and SP1/Angptl7 signaling may play key roles in this process. This research aimed to investigate whether Platelet-derived growth factor (PDGF)-BB regulates chondro-endothelial crosstalk via Piezo1-mediated SP1/Angptl7 inhibition.
Methods:
Single- and multiple-cell-component organoids (chondrocytes SW1353 and endothelial HMEC-1) were constructed using high-throughput 3D culture. Organoids were treated with MIA to induce OA-like changes, followed by PDGF-BB with or without Yoda1 (Piezo1 activator) or Angptl7. In vivo, OA was induced in rats by intraarticular MIA injection, and PDGF-BB or sodium hyaluronate (SH)-PDGF was administered. Histology and immunofluorescence were used to assess F-actin formation, Piezo1 activation, SP1 phosphorylation, Angptl7 and VEGF/Notch/DLL4 expression.
Results:
PDGF-BB inhibited F-actin formation and reduced Piezo1 activation in OA chondrocytes. It suppressed SP1 phosphorylation and Angptl7 expression, downregulating VEGF/Notch/DLL4 signaling and reducing endothelial invasion in organoids. These effects were partially reversed by Yoda1 and fully reversed by Angptl7. In vivo, PDGF-BB and SH-PDGF attenuated cartilage degeneration and reduced Piezo1 activation, SP1 phosphorylation, and Angptl7 expression.
Discussion:
PDGF-BB alleviates OA by inhibiting SP1/Angptl7-mediated chondro-endothelial crosstalk, partially via stress-sensitive Piezo1 regulation through cytoskeletal remodeling. Multiple-cell-component organoids provide a valuable in vitro model for studying cartilage pathophysiology.
Insights
Platelet-derived growth factor-BB (PDGF-BB) alleviates osteoarthritis by inhibiting SP1/Angptl7 signaling via Piezo1, reducing chondro-endothelial crosstalk. This study highlights PDGF-BB
Area of Science:
- Biomedical Engineering
- Cell Biology
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is characterized by cartilage degradation and subchondral bone changes.
- Mechanisms of chondro-endothelial crosstalk in OA are not fully understood.
- Piezo1 channels and SP1/Angptl7 signaling are implicated in OA pathogenesis.
Purpose of the Study:
- To investigate the role of Platelet-derived growth factor (PDGF)-BB in regulating chondro-endothelial crosstalk.
- To determine if PDGF-BB acts via Piezo1-mediated inhibition of SP1/Angptl7 signaling.
- To explore the therapeutic potential of PDGF-BB in OA models.
Main Methods:
- Construction of single- and multiple-cell-component organoids using 3D culture.
- Induction of OA-like changes using MIA and treatment with PDGF-BB, Yoda1, or Angptl7.
- In vivo OA model in rats treated with PDGF-BB or SH-PDGF, followed by histological and immunofluorescence analysis.
Main Results:
- PDGF-BB inhibited F-actin formation and Piezo1 activation in OA chondrocytes, suppressing SP1 phosphorylation and Angptl7 expression.
- PDGF-BB downregulated VEGF/Notch/DLL4 signaling, reducing endothelial invasion in organoids.
- In vivo, PDGF-BB and SH-PDGF attenuated cartilage degeneration and key molecular markers of OA.
Conclusions:
- PDGF-BB alleviates OA by inhibiting SP1/Angptl7-mediated chondro-endothelial crosstalk.
- This effect is partly mediated by Piezo1 regulation through cytoskeletal remodeling.
- Multi-component organoids serve as a valuable in vitro model for OA research.
