Bone marrow neutrophil aging in sickle cell disease mice is associated with impaired osteoblast functions

Autor: Kimberly Pantoja, Liping Xiao, Kavita Rana
Rok vydání: 2018
Předmět:
Zdroj: Biochemistry and Biophysics Reports, Vol 16, Iss, Pp 110-114 (2018)
Biochemistry and Biophysics Reports
ISSN: 2405-5808
DOI: 10.1016/j.bbrep.2018.10.009
Popis: Bone loss is a common complication in individuals with sickle cell disease (SCD). The mechanism(s) of bone loss in SCD subjects has not been fully investigated, and there are no targeted therapies to prevent or treat compromised bone health in this population. Recent studies showed that depletion of gut microbiota with antibiotics significantly reduced the number of aged neutrophils, thereby dramatically improved the inflammation-related organ damages in SCD mice. Since neutrophils, abundantly present in bone marrow (BM), regulate bone cells, and BM neutrophils, induced by inflammatory cytokines, are associated with a low number of osteoblasts (OBs), we hypothesize that neutrophil aging in the BM of SCD mice impairs OB function. Flow cytometry analysis showed BM neutrophil aging was significantly increased in SCD mice that was reduced with antibiotic treatment. In vitro co-culture of calvarial OBs from control (Ctrl) mice with BM neutrophils from Ctrl or SCD mice showed that BM neutrophils from SCD mice inhibit OB function but was rescued when neutrophils were from antibiotic-treated SCD mice. In summary, there is an accumulation of aged neutrophils in BM from SCD mice that may contribute to impaired OB function, and antibiotic treatment is able to partially rescue impaired OB function by decreasing neutrophil aging in the BM of SCD mice.
Highlights • There is increased neutrophil ageing in bone marrow of sickle cell disease mice. • Bone marrow neutrophils in sickle cell disease mice impair osteoblast function. • Antibiotics rescue the osteoblast dysfunctions by decreasing aged neutrophils.
Databáze: OpenAIRE