Dell'Accio, Franceso

Francesco Dell'Accio

Professor of Musculoskeletal Regenerative Medicine & Rheumatology

Professor Dell’Accio is a clinical rheumatologist and a scientist whose interest is focused in cartilage biology. He has been active in the field of cartilage repair by and autologous chondrocyte transplantation. Moving to the UK in 2003 he unveiled the molecular cascade activated by injury to the articular cartilage. His current research aims at understanding the role that individual signaling molecules in cartilage wound healing and homeostatic responses, with the ultimate goal to develop pharmacological interventions to restore cartilage integrity.

Summary of Research

Professor Dell’Accio and his group investigate the molecular mechanisms that preside to the healing of skeletal tissues, and in particular to cartilage, with the ultimate aim of identifying possible therapeutic intervention to promote cartilage healing/supporting cartilage homeostasis in diseases such as isolated cartilage defects and osteoarthritis. Professor Dell’Accio’s group identified a distinct signalling response of adult human articular cartilage to mechanical injury. Individual signalling molecules and signalling pathways identified by this screening are being tested in vitro and in vivo for their function in cartilage biology and joint surface repair.  In vivo models include surgical models of osteoarthritis (destabilization of the medial meniscus (DMM) or a novel model of mechanical cartilage injury and regeneration developed in our laboratory. He is now exploring on one hand the biological function of such mechanism for cartilage homeostasis, and on the other hand how we can exploit it to protect cartilage from degradation in arthritis.

Research highlights

  • WNT molecules can signal simultaneously through multiple, reciprocally inhibitory pathways, with distinctive outcomes (Nalesso et al. J Cell Biol 2011)
  • WNT16, a molecule that contributes to joint specification during embryogenesis, contributes to the homeostatic response to joint injury in adulthood. Nalesso, Thomas et al. Ann Rheum Dis 2016)
  • The chemokine receptor CXCR2 is expressed in chondrocytes and its function is essential in cartilage homeostasis and injury response in a AKT-dependent manner. (Sherwood et al. Ann Rheum Dis 2015)
  • Agrin is an extracellular proteoglycan expressed in cartilage and a potent chondrogenic factor (Eldridge et al. Ann Rheum Dis 2015).
Articular cartilage under polarized light microscopy
Articular cartilage under polarized light microscopy

Members of the Group

  • Dr Suzanne Eldridge
  • Dr Mario Alvarez
  • Dr Bethan Thomas
  • Miss Anne-Sophie Thorup (PhD student)
  • Dr. Sara Caxaria
  • Dr Kiran Peddireddi (Technician)
  • Miss Aida Barawi (Technician)

Key Publications

For a full list of publist publications click here

Nalesso G, Thomas BL, Sherwood JC, Yu J, Addimanda O, Eldridge SE, Thorup AS, Dale L, Schett G, Zwerina J, Eltawil N, Pitzalis C, Dell'Accio F. WNT16 antagonises excessive canonical WNT activation and protects cartilage in osteoarthritis. Ann Rheum Dis. 2017 Jan;76(1):218-226. doi: 10.1136/annrheumdis-2015-208577. PubMed PMID: 27147711.

Wei W, Bastiaansen-Jenniskens YM, Suijkerbuijk M, Kops N, Bos PK, Verhaar JA, Zuurmond AM, Dell'Accio F, van Osch GJ. High-fat diet accelerates cartilage repair in DBA/1 mice. J Orthop Res. 2016 May 4. doi: 10.1002/jor.23280. [Epub ahead of print] PubMed PMID: 27147295.

Headland SE, Jones HR, Norling LV, Kim A, Souza PR, Corsiero E, Gil CD, Nerviani A, Dell'Accio F, Pitzalis C, Oliani SM, Jan LY, Perretti M. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Sci Transl Med. 2015 Nov 25;7(315):315ra190. doi: 10.1126/scitranslmed.aac5608. PubMed PMID: 26606969.

Eldridge S, Nalesso G, Ismail H, Vicente-Greco K, Kabouridis P, Ramachandran M, Niemeier A, Herz J, Pitzalis C, Perretti M, Dell'Accio F. Agrin mediates chondrocyte homoeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo. Ann Rheum Dis. 2016 Jun;75(6):1228-35. doi: 10.1136/annrheumdis-2015-207316. PubMed PMID: 26290588; PubMed Central PMCID: PMC4760904.

Sherwood J, Bertrand J, Nalesso G, Poulet B, Pitsillides A, Brandolini L, Karystinou A, De Bari C, Luyten FP, Pitzalis C, Pap T, Dell'Accio F. A homeostatic function of CXCR2 signalling in articular cartilage. Ann Rheum Dis. 2015 Dec;74(12):2207-15. doi: 10.1136/annrheumdis-2014-205546. PubMed PMID: 25135253; PubMed Central PMCID: PMC4680121.

Lin NY, Distler A, Beyer C, Philipi-Schöbinger A, Breda S, Dees C, Stock M, Tomcik M, Niemeier A, Dell'Accio F, Gelse K, Mattson MP, Schett G, Distler JH. Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis. Ann Rheum Dis. 2016 Nov;75(11):2037-2044. doi: 10.1136/annrheumdis-2015-208420. PubMed PMID: 26851274.

Heywood HK, Nalesso G, Lee DA, Dell'accio F. Culture expansion in low-glucose conditions preserves chondrocyte differentiation and enhances their subsequent capacity to form cartilage tissue in three-dimensional culture. Biores Open Access. 2014 Feb 1;3(1):9-18. doi: 10.1089/biores.2013.0051. PubMed PMID: 24570841; PubMed Central PMCID: PMC3929268.

Bertrand J, Stange R, Hidding H, Echtermeyer F, Nalesso G, Godmann L, Timmen M, Bruckner P, Dell'Accio F, Raschke MJ, Pap T, Dreier R. Syndecan 4 supports bone fracture repair, but not fetal skeletal development, in mice. Arthritis Rheum. 2013 Mar;65(3):743-52. doi: 10.1002/art.37817. PubMed PMID: 23233348.

Bertrand J, Nitschke Y, Fuerst M, Hermann S, Schäfers M, Sherwood J, Nalesso G, Ruether W, Rutsch F, Dell'Accio F, Pap T. Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are associated with cartilage calcification in osteoarthritis and trigger osteoarthritic changes in mice. Ann Rheum Dis. 2012 Jul;71(7):1249-53. doi: 10.1136/annrheumdis-2011-200892. PubMed PMID: 22510396.

Kurth TB, Dell'accio F, Crouch V, Augello A, Sharpe PT, De Bari C. Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo. Arthritis Rheum. 2011 May;63(5):1289-300. doi: 10.1002/art.30234. PubMed PMID: 21538315.

Nalesso G, Sherwood J, Bertrand J, Pap T, Ramachandran M, De Bari C, Pitzalis C, Dell'accio F. WNT-3A modulates articular chondrocyte phenotype by activating both canonical and noncanonical pathways. J Cell Biol. 2011 May 2;193(3):551-64.  doi: 10.1083/jcb.201011051. PubMed PMID: 21536751; PubMed Central PMCID: PMC3087013.

Hughes C, Faurholm B, Dell'Accio F, Manzo A, Seed M, Eltawil N, Marrelli A, Gould D, Subang C, Al-Kashi A, De Bari C, Winyard P, Chernajovsky Y, Nissim A. Human single-chain variable fragment that specifically targets arthritic cartilage. Arthritis Rheum. 2010 Apr;62(4):1007-16. doi: 10.1002/art.27346. PubMed PMID: 20131274; PubMed Central PMCID: PMC2905615.

Dell'accio F, De Bari C, Eltawil NM, Vanhummelen P, Pitzalis C. Identification of the molecular response of articular cartilage to injury, by microarray screening: Wnt-16 expression and signalling after injury and in osteoarthritis. Arthritis Rheum. 2008 May;58(5):1410-21. doi:10.1002/art.23444. PubMed PMID: 18438861.

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