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Bone. 2017 Oct;103:1-11. doi: 10.1016/j.bone.2017.06.004. Epub 2017 Jun 7.

Splenomegaly, myeloid lineage expansion and increased osteoclastogenesis in osteogenesis imperfecta murine.

Author information

1
Department of Reconstructive Sciences, University of Connecticut, Farmington, CT 06030, USA. Electronic address: brya.g.matthews@gmail.com.
2
Department of Reconstructive Sciences, University of Connecticut, Farmington, CT 06030, USA.
3
Department of Immunology, University of Connecticut, Farmington, CT 06030, USA.
4
Center on Aging, University of Connecticut, Farmington, CT 06030, USA.
5
Department of Physiology and Immunology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia.
6
Department of Reconstructive Sciences, University of Connecticut, Farmington, CT 06030, USA. Electronic address: ikalaj@uchc.edu.

Abstract

Osteogenesis imperfecta (OI) is a disease caused by defects in type I collagen production that results in brittle bones. While the pathology is mainly caused by defects in the osteoblast lineage, there is also elevated bone resorption by osteoclasts resulting in high bone turnover in severe forms of the disease. Osteoclasts originate from hematopoietic myeloid cells, however changes in hematopoiesis have not been previously documented in OI. In this study, we evaluated hematopoietic lineage distribution and osteoclast progenitor cell frequency in bone marrow, spleen and peripheral blood of osteogenesis imperfecta murine (OIM) mice, a model of severe OI. We found splenomegaly in all ages examined, and expansion of myeloid lineage cells (CD11b+) in bone marrow and spleen of 7-9week old male OIM animals. OIM spleens also showed an increased frequency of purified osteoclast progenitors. This phenotype is suggestive of chronic inflammation. Isolated osteoclast precursors from both spleen and bone marrow formed osteoclasts more rapidly than wild-type controls. We found that serum TNFα levels were increased in OIM, as was IL1α in OIM females. We targeted inflammation therapeutically by treating growing animals with murine TNFR2:Fc, a compound that blocks TNFα activity. Anti-TNFα treatment marginally decreased spleen mass in OIM females, but failed to reduce bone resorption, or improve bone parameters or fracture rate in OIM animals. We have demonstrated that OIM mice have changes in their hematopoietic system, and form osteoclasts more rapidly even in the absence of OI osteoblast signals, however therapy targeting TNFα did not improve disease parameters.

KEYWORDS:

Inflammation; Osteoclast; Osteogenesis imperfecta; Tumor necrosis factor alpha

PMID:
28600151
PMCID:
PMC5764163
DOI:
10.1016/j.bone.2017.06.004
[Indexed for MEDLINE]
Free PMC Article

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