AB0039 AGRIN REPAIRS BONE AND CARTILAGE IN VIVO

Background: Cartilage defects in the joints are reported 61% of all arthroscopies 1&2 . The size cartilage repair market is estimated to be $2.195 million by 2025 3 can evolve into osteoarthritis, which abnormal load results breakdown, joint pain and reduced mobility. Osteoarthritis leading cause permanent disability absenteeism affects up 1/3 people over 60yrs. In western countries osteoarthritis costs 1.5-2% GDP 4 Joint replacement with a prosthesis restores some degree independence but 20% patients it does not meet expectations 5 has limited life span. There no pharmacological intervention that arrests or reverts course despite desperate need. We previously published agrin plays an important role homeostasis 6 addition chondrocytes vivo resulted enhanced formation, suggesting potential for repair. Objectives: Investigate use Methods: Critical osteochondral were generated mice sheep injected intraarticularly type I collagen gel containing vehicle. Animals monitored 8 weeks months respectively. MicroCT, histological analysis, qPCR, linage tracking, reporter assays, chondrogenesis assay, immunohistochemistry performed. Results: A single intraarticular administration induced regeneration critical-size mice, restoring tissue architecture bone-cartilage interface. Agrin stem cells site injury and, through simultaneous activation CREB suppression canonical WNT signalling, GDF5 expression differentiation stable articular chondrocytes, forming cartilage. sheep, treatment bone cartilage, promoted increased ambulatory activity. Conclusion: orchestrates morphogenesis at surface modulating multiple signalling pathways, supporting therapeutic regeneration. References: [1]Curl, W. et al. injuries: review 31,516 knee arthroscopies. Arthrosc. J. Relat. Surg. Off. Publ. Assoc. N. Am. Int. 13, 456–460 (1997). [2]Hjelle, K., Solheim, E., Strand, T., Muri, R. & Brittberg, M. Articular 1,000 18, 730–734 (2002). [3]Cartilage Repair Market Size, Share, Industry Analysis 2018-2025 | AMR. Allied Research https://www.alliedmarketresearch.com/cartilage-repair-market [4]Hiligsmann, Health economics field osteoarthritis: expert’s consensus paper from European Society Clinical Economic Aspects Osteoporosis (ESCEO). Semin. Arthritis Rheum. 43, 303–313 (2013). [5]Dieppe, P., Lim, K. Lohmander, S. Who should have surgery osteoarthritis? Dis. 14, 175–180 (2011). [6]Eldridge, S., mediates chondrocyte requires both LRP4 α-dystroglycan enhance formation vitro vivo. Annals rheumatic diseases 75 (6), 1228-1235 (2016). Acknowledgements: thank technical staff ARM Lab Staff University Aberdeen’s Animal Facility Microscopy Histology support. Funding: gratefully acknowledge funding support this work MRC (MR/L022893/1, MR/N010973/1,and MR/P026362/1), Versus (19667, 21515, 20886, 21621), Rosetrees Trust (A1205), Medical College St Bartholomew’s Hospital Trust, William Harvey Foundation. Disclosure Interests: Suzanne Eldridge: None declared, Aida Barawi: Hui Wang: Anke Roelofs: Magdalena Kaneva: Zeyu Guan: Helen Lydon: Bethan Thomas: Anne-Sophie Thorup: Beatriz F Fernandez: Sara Caxaria: Danielle Strachan: Ahmed Ali: Kanatheepan Shanmuganathan: Costantino Pitzalis: James Whiteford: Fran Henson: Andrew McCaskie: Cosimo De Bari: Francesco Dell’Accio Consultant of: F.D. received consultancy fees Samumed UCB.