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Tendon stem\/progenitor cells (TSPCs) are vital for tendon repair, with their stemness crucial to healing outcomes. This study investigated the role of CD248 in regulating TSPC stemness and assessed the therapeutic potential of si\u2010CD248\u2010loaded liposomes in promoting tendon\u2010bone healing under osteoporotic conditions. Single\u2010cell RNA sequencing (scRNA\u2010seq) identified increased TSPC populations, particularly a unique subcluster, TSPC\u20100, with elevated CD248 expression in osteoporotic tendon samples. CD248\n                    <jats:sup>+<\/jats:sup>\n                    TSPCs displayed reduced proliferation, increased apoptosis, and impaired migration, driven by altered FAK\u2010JAK\u2010STAT1 signaling. si\u2010CD248\u2010loaded liposomes were formulated and characterized, demonstrating efficacy in inhibiting CD248 expression, restoring TSPC stemness, and promoting tendon\u2010bone healing. In osteoporotic mice, liposome treatment significantly enhanced tissue regeneration, improving histological scores, collagen organization, and biomechanical properties. This study reveals that elevated CD248 expression negatively impacts TSPC stemness and impairs healing under osteoporotic conditions. Targeting CD248 using si\u2010CD248\u2010loaded liposomes effectively restores TSPC regenerative potential, representing a promising therapeutic strategy to enhance tendon\u2010bone healing in osteoporotic patients.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509883","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T10:06:58Z","timestamp":1750327618000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bioactive siRNA\u2010Based Liposomes Promoted Tendon\u2010Bone Healing in Osteoporotic Mice by Recovering the Stemness of CD248\n                    <sup>+<\/sup>\n                    TSPCs"],"prefix":"10.1002","volume":"12","author":[{"given":"Yinhua","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Orthopedics Kunshan Hospital of Chinese Medicine\uff0cKunshan Hospital Affiliated to Nanjing University of Chinese Medicine  No.388 Zuchongzhi South 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