{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:07:16Z","timestamp":1784092036961,"version":"3.55.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , PDGF-BB and SH-PDGF attenuated cartilage degeneration and reduced Piezo1 activation, SP1 phosphorylation, and Angptl7 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>in vitro<\/jats:italic>\n                      model for studying cartilage pathophysiology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1853487","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:39:42Z","timestamp":1784090382000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PDGF-BB inhibits SP1\/Angptl7 mediated chondro-endothelial crosstalk via stress-sensitivity Piezo1 regulation in osteoarthritis"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhengchao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Sports Medicine, Wuhan Fourth Hospital","place":["Wuhan, China"]},{"name":"Hubei Provincial Sports Medicine Center","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Sports Injury and Precision Treatment, Wuhan Fourth Hospital","place":["Wuhan, China"]},{"name":"Hubei Provincial Clinical Research Center for Orthopaedics","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangxia","family":"Cheng","sequence":"additional","affiliation":[{"name":"Hubei Provincial Sports Medicine Center","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Sports Injury and Precision Treatment, Wuhan Fourth Hospital","place":["Wuhan, China"]},{"name":"Hubei Provincial Clinical Research Center for Orthopaedics","place":["Wuhan, China"]},{"name":"Department of Anesthesiology, Wuhan Fourth Hospital","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Zibo First Hospital, Zibo Prevention and Treatment Hospital for Occupation Diseases","place":["Zibo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Wuhan Fourth Hospital","place":["Wuhan, China"]},{"name":"Hubei Provincial Sports Medicine Center","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Sports Injury and Precision Treatment, Wuhan Fourth Hospital","place":["Wuhan, China"]},{"name":"Hubei Provincial Clinical Research Center for Orthopaedics","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hubei Provincial Sports Medicine Center","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Sports Injury and Precision Treatment, Wuhan Fourth Hospital","place":["Wuhan, China"]},{"name":"Hubei Provincial Clinical Research Center for Orthopaedics","place":["Wuhan, China"]},{"name":"Department of Cardiovascular, Wuhan Fourth Hospital","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Cai","sequence":"additional","affiliation":[{"name":"Hubei Provincial Sports Medicine Center","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Sports Injury and Precision Treatment, Wuhan Fourth Hospital","place":["Wuhan, China"]},{"name":"Hubei Provincial Clinical Research Center for Orthopaedics","place":["Wuhan, China"]},{"name":"Department of Rehabilitation, Wuhan Fourth Hospital","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1038\/s41467-023-36408-0","article-title":"Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect","volume":"14","author":"Abe","year":"2023","journal-title":"Nat. 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