4.8 Article

Agrin induces long-term osteochondral regeneration by supporting repair morphogenesis

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SCIENCE TRANSLATIONAL MEDICINE
卷 12, 期 559, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aax9086

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资金

  1. MRC [MR/L022893/1, MR/N010973/1, MR/P026362/1]
  2. Versus Arthritis [19667, 21515, 20886, 21621]
  3. Rosetrees Trust [A1205]
  4. Medical College of St Bartholomew's Hospital Trust
  5. William Harvey Research Foundation
  6. MRC [MC_PC_17230, MR/R000956/1, MR/L022893/1, MR/N010973/1, MR/P026362/1, MR/R015635/1, MR/K013076/1] Funding Source: UKRI

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Cartilage loss leads to osteoarthritis, the most common cause of disability for which there is no cure. Cartilage regeneration, therefore, is a priority in medicine. We report that agrin is a potent chondrogenic factor and that a single intraarticular administration of agrin induced long-lasting regeneration of critical-size osteochondral defects in mice, with restoration of tissue architecture and bone-cartilage interface. Agrin attracted joint resident progenitor cells to the site of injury and, through simultaneous activation of CREB and suppression of canonical WNT signaling downstream of beta-catenin, induced expression of the chondrogenic stem cell marker GDF5 and differentiation into stable articular chondrocytes, forming stable articular cartilage. In sheep, an agrin-containing collagen gel resulted in long-lasting regeneration of bone and cartilage, which promoted increased ambulatory activity. Our findings support the therapeutic use of agrin for joint surface regeneration.

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