Key result
PDGF-BB alleviates osteoarthritis by blocking Piezo1- and Angptl7-mediated chondro-endothelial crosstalk.
Why the study?
The mechanisms underlying chondro-endothelial crosstalk in osteoarthritis remain unclear, including the potential roles of stress-sensitive Piezo1 and SP1/Angptl7 signaling.
Does PDGF-BB alleviate osteoarthritis by inhibiting chondro-endothelial crosstalk in in vitro and in vivo models?
Does PDGF-BB alleviate osteoarthritis by inhibiting chondro-endothelial crosstalk in in vitro and in vivo models?
PDGF-BB alleviates osteoarthritis by inhibiting SP1/Angptl7-mediated chondro-endothelial crosstalk via stress-sensitive Piezo1 regulation, offering a potential therapeutic mechanism.
No immediate clinical implications in OA; leaves open Piezo1/SP1/Angptl7 as targets pending in vivo validation.
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.
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Wang et al. (2026) studied Osteoarthritis. PDGF-BB vs. Saline was evaluated on Cartilage degeneration and chondro-endothelial crosstalk. PDGF-BB alleviates osteoarthritis by inhibiting SP1/Angptl7-mediated VEGF/Notch/DLL4 chondro-endothelial crosstalk, partially through stress-sensitive Piezo1 inhibition via F-actin regulation.
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