Targeting angiogenesis for fracture nonunion treatment in inflammatory disease.

Bone Research
Cuicui WangJie Shen

Abstract

Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions. In this study, we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheumatoid arthritis (RA). Arthritic mice displayed fracture nonunion with the absence of fracture callus, diminished angiogenesis and fibrotic scar tissue formation leading to the failure of biomechanical properties, representing the major manifestations of atrophic nonunion in the clinic. Mechanistically, we demonstrated that the angiogenesis defect observed in RA mice was due to the downregulation of SPP1 and CXCL12 in chondrocytes, as evidenced by the restoration of angiogenesis upon SPP1 and CXCL12 treatment in vitro. In this regard, we developed a biodegradable scaffold loaded with SPP1 and CXCL12, which displayed a beneficial effect on angiogenesis and fracture repair in mice despite the presence of inflammation. Hence, these findings strongly suggest that the sustained release of SPP1 and CXCL12 represents an effective therapeutic approach to treat impaired angiogenesis and fracture nonunion under inflammatory conditions.

References

Jun 1, 1995·The Journal of Bone and Joint Surgery. American Volume·T A Einhorn
Apr 21, 1995·Annals of the New York Academy of Sciences·J SodekR H Kim
Oct 1, 1994·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·K HirakawaS Nomura
Apr 1, 1996·British Journal of Rheumatology·A A Deodhar, A D Woolf
Jul 24, 1998·Journal of Biomechanical Engineering·E UchiyamaT Sasaki
Jan 26, 1999·Clinical Orthopaedics and Related Research·J Glowacki
May 13, 1999·Journal of Biomedical Materials Research·J O HollingerD Buck
Jul 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·John StreetEllen H Filvaroff
Sep 13, 2003·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Mikihiko MorinobuMasaki Noda
May 3, 2005·The Journal of Clinical Investigation·Kathryn E Wellen, Gökhan S Hotamisligil
Nov 18, 2005·Injury·Panagiotis Megas, Megas Panagiotis
Apr 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·M Brett EverhartTimothy S Blackwell
Aug 18, 2006·The New England Journal of Medicine·D L Scott, G H Kingsley
Nov 8, 2006·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Craig L DuvallRobert E Guldberg
Dec 7, 2007·The Journal of Surgical Research·Patric GarciaMichael D Menger
Dec 25, 2007·Journal of Theoretical Biology·Liesbet GerisHans Van Oosterwyck
May 9, 2008·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Chuanyong LuRalph S Marcucio
Oct 14, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Amish A NaikRegis J O'Keefe
Mar 11, 2009·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jasmin LienauHanna Schell
Nov 6, 2009·Blood·Frank C CackowskiG David Roodman
Jul 6, 2010·Journal of Cellular and Molecular Medicine·Pieter H AnborghAnn F Chambers
Sep 15, 2010·Cancer Metastasis Reviews·Xueqing SunJianhua Wang
Dec 17, 2010·Current Pharmaceutical Design·S LiekensS Hatse
Jan 5, 2011·Cell Metabolism·Rebecca G BakerSankar Ghosh
Jan 7, 2011·Journal of Leukocyte Biology·Okan BastianTaco Blokhuis
Jan 22, 2011·Nature Reviews. Immunology·Noriyuki OuchiKenneth Walsh
Jul 7, 2011·European Cells & Materials·M FassbenderB Wildemann
Dec 14, 2011·The New England Journal of Medicine·Iain B McInnes, Georg Schett
Feb 2, 2012·Nature Reviews. Rheumatology·Lutz ClaesAnita Ignatius
May 18, 2012·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Chrisoula A ToupadakisClare E Yellowley
Jun 27, 2012·The Journal of Bone and Joint Surgery. British Volume·L A Mills, A H R W Simpson
Feb 20, 2013·Nature Reviews. Rheumatology·Ernest H ChoySimon A Jones

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