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Neurogenic Heterotopic Ossifications Develop Independently of Granulocyte Colony‐Stimulating Factor and Neutrophils
Journal of bone and mineral research, 2020-11, Vol.35 (11), p.2242-2251
Tseng, Hsu‐Wen
Kulina, Irina
Salga, Marjorie
Fleming, Whitney
Vaquette, Cedryck
Genêt, François
Levesque, Jean‐Pierre
Alexander, Kylie A
2020
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Tseng, Hsu‐Wen
Kulina, Irina
Salga, Marjorie
Fleming, Whitney
Vaquette, Cedryck
Genêt, François
Levesque, Jean‐Pierre
Alexander, Kylie A
Titel
Neurogenic Heterotopic Ossifications Develop Independently of Granulocyte Colony‐Stimulating Factor and Neutrophils
Ist Teil von
Journal of bone and mineral research, 2020-11, Vol.35 (11), p.2242-2251
Ort / Verlag
Hoboken, USA: John Wiley & Sons, Inc
Erscheinungsjahr
2020
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
ABSTRACT Neurogenic heterotopic ossifications (NHOs) are incapacitating heterotopic bones in periarticular muscles that frequently develop following traumatic brain or spinal cord injuries (SCI). Using our unique model of SCI‐induced NHO, we have previously established that mononucleated phagocytes infiltrating injured muscles are required to trigger NHO via the persistent release of the pro‐inflammatory cytokine oncostatin M (OSM). Because neutrophils are also a major source of OSM, we investigated whether neutrophils also play a role in NHO development after SCI. We now show that surgery transiently increased granulocyte colony‐stimulating factor (G‐CSF) levels in blood of operated mice, and that G‐CSF receptor mRNA is expressed in the hamstrings of mice developing NHO. However, mice defective for the G‐CSF receptor gene Csf3r, which are neutropenic, have unaltered NHO development after SCI compared to C57BL/6 control mice. Because the administration of recombinant human G‐CSF (rhG‐CSF) has been trialed after SCI to increase neuroprotection and neuronal regeneration and has been shown to suppress osteoblast function at the endosteum of skeletal bones in human and mice, we investigated the impact of a 7‐day rhG‐CSF treatment on NHO development. rhG‐CSF treatment significantly increased neutrophils in the blood, bone marrow, and injured muscles. However, there was no change in NHO development compared to saline‐treated controls. Overall, our results establish that unlike monocytes/macrophages, neutrophils are dispensable for NHO development following SCI, and rhG‐CSF treatment post‐SCI does not impact NHO development. Therefore, G‐CSF treatment to promote neuroregeneration is unlikely to adversely promote or affect NHO development in SCI patients. © 2020 American Society for Bone and Mineral Research.
Sprache
Englisch
Identifikatoren
ISSN: 0884-0431
eISSN: 1523-4681
DOI: 10.1002/jbmr.4118
Titel-ID: cdi_hal_primary_oai_HAL_hal_03032283v1
Format
–
Schlagworte
ANIMAL MODELS
,
Bone marrow
,
Bones
,
Cerebrospinal fluid
,
Colonies
,
CYTOKINES
,
DISEASES AND DISORDERS OF/RELATED TO BONE (OTHER)
,
Granulocytes
,
Inflammation
,
Leukocytes (granulocytic)
,
Leukocytes (neutrophilic)
,
Life Sciences
,
Macrophages
,
Monocytes
,
mRNA
,
Muscles
,
Neuroprotection
,
Neutropenia
,
Neutrophils
,
Oncostatin M
,
OSTEOIMMUNOLOGY
,
Phagocytes
,
Regeneration
,
Spinal cord injuries
,
Surgery
,
Traumatic brain injury
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