Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease.

Blood
Luca Dalle CarbonareLucia De Franceschi

Abstract

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects a large part of the SCD patient population, and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in a humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment, with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL), and osteoclast recruitment (Rank) with upregulation of IL-6 as proresorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). To interfere with the development of SBD, zoledronic acid (Zol), a potent inhibitor of osteoclast activity/osteoclastogenesis and promoter of osteogenic lineage, was used in H/R-exposed mice. Zol markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc), and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast r...Continue Reading

References

Jan 1, 1990·Advances in Protein Chemistry·W A Eaton, J Hofrichter
Jun 22, 2000·The New England Journal of Medicine·O S Platt
Jan 10, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·L Dalle CarbonareP J Meunier
May 10, 2005·British Journal of Haematology·Antonio Almeida, Irene Roberts
Dec 1, 2005·Pediatric Blood & Cancer·Ashutosh LalElliott P Vichinsky
Mar 22, 2006·American Journal of Hematology·Redonda G MillerSophie Lanzkron
Sep 5, 2006·Reviews in Endocrine & Metabolic Disorders·Angela Bruzzaniti, Roland Baron
Jan 17, 2007·British Journal of Haematology·Mona SarraiRita Bellevue
Feb 5, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lucia De FranceschiCarlo Brugnara
Apr 3, 2008·The Journal of Clinical Investigation·Nathalie SabaaPierre-Louis Tharaux
May 27, 2008·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·R P Hebbel
Jun 24, 2008·Bulletin of the World Health Organization·Bernadette Modell, Matthew Darlison
Sep 16, 2009·Cardiovascular & Hematological Disorders Drug Targets·Robert P HebbelKarl A Nath
Jul 27, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Sara M Mantila RoosaCharles H Turner
Aug 27, 2010·Arthritis Research & Therapy·Maria Teresa ValentiLuca Dalle Carbonare
Apr 2, 2011·Seminars in Thrombosis and Hemostasis·Lucia De FranceschiOliviero Olivieri
May 7, 2011·Haematologica·Mehdi NouraieVictor R Gordeuk
Jan 1, 2010·Drug, Healthcare and Patient Safety·Luca Dalle CarbonareMaria Teresa Valenti
Oct 19, 2011·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·F S NevesI Crusoé-Rebello
May 5, 2012·The Journal of Biological Chemistry·Guozhi XiaoChuanyue Wu
Dec 1, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·David W DempsterA Michael Parfitt
Oct 24, 2013·Current Opinion in Endocrinology, Diabetes, and Obesity·Ifeyinwa Osunkwo
May 2, 2014·Nature Communications·Shoshana M BartellMaria Almeida
Mar 10, 2015·Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer·Ibrahim SehitogluErkan Cure

❮ Previous
Next ❯

Citations

May 20, 2016·Proteomics. Clinical Applications·Raffaele Renella
Nov 25, 2016·Animal : an International Journal of Animal Bioscience·E PaludoM C Ledur
Dec 31, 2016·International Journal of Molecular Sciences·Maria Teresa ValentiMonica Mottes
Jun 14, 2017·International Journal of Molecular Sciences·Luca Dalle CarbonareMaria Teresa Valenti
Apr 19, 2018·Journal of Pediatric Hematology/oncology·Kristen M WilliamsIlene Fennoy
Sep 27, 2018·American Journal of Hematology·Elisabetta BeneduceLucia De Franceschi
Nov 14, 2015·Blood·Victor R Gordeuk
Mar 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria Teresa ValentiLuca Dalle Carbonare
May 31, 2019·Orphanet Journal of Rare Diseases·Giovanna RussoGian Luca Forni
Feb 26, 2021·Haematologica·Slimane AllaliMariane de de Montalembert
Mar 7, 2021·International Journal of Environmental Research and Public Health·Paola GiordanoMaria Felicia Faienza
Apr 7, 2021·The Journal of Clinical Investigation·Alessandro MatteLucia De Franceschi
Aug 10, 2021·Oral Diseases·Susilena Arouche CostaSoraia de Fátima Carvalho Souza

❮ Previous
Next ❯

Related Concepts

Related Feeds

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.