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Absence of complement factor H alters bone architecture and dynamics.
- Source :
-
Immunobiology [Immunobiology] 2018 Dec; Vol. 223 (12), pp. 761-771. Date of Electronic Publication: 2018 Aug 01. - Publication Year :
- 2018
-
Abstract
- Complement system is an important arm of the immune system that promotes inflammation. Complement Factor H (FH) is a critical regulator of the alternative complement pathway. Its absence causes pathology in different organs resulting in diseases such as age related macular degeneration and dense deposit disease. Recent studies suggest that the complement system plays a role in bone development and homeostasis. To determine the role of FH in bone architecture, we studied the FH knockout (fh-/-) mice. 3D reconstructions of femur from 16 week old fh-/- mice reveal significant changes, such as decreased BV/TV (4.5%, p < 0.02), trabecular number (22%, p < 0.01), tissue mineral density (16%, p < 0.04), and increased marrow area (16% p < 0.01), compared to their wild type (WT) counterparts. Kidney function and histology remained normal indicating that bone changes occurred prior to kidney dysfunction. Next we examined cultured osteoblasts and osteoclasts isolated from bone marrow. FH is expressed ubiquitously in the osteoblasts and in the cytoplasm of osteoclasts. The changes caused by absence of FH include: increase in number of osteoblasts (362%) and osteoclasts (342%), increase in RNA (180%) and protein expression of cathepsin K and increased osteoclast function (pit formation, 233%). Actin rearrangement in both osteoblasts and osteoclasts was altered, with a loss of integrity of the F-actin ring at the periphery of the osteoclasts. For the first time our studies demonstrate a direct role of FH in the maintenance of bone structure and function and is highlighted as a promising therapeutic target in bone diseases.<br /> (Copyright © 2018 Elsevier GmbH. All rights reserved.)
- Subjects :
- Actins metabolism
Animals
Biomarkers
Bone Resorption genetics
Bone Resorption metabolism
Bone Resorption pathology
Bone and Bones diagnostic imaging
Bone and Bones pathology
Complement Factor H genetics
Complement Factor H metabolism
Fluorescent Antibody Technique
Immunohistochemistry
Mice
Mice, Knockout
Osteoblasts immunology
Osteoblasts metabolism
Osteoclasts immunology
Osteoclasts metabolism
Phenotype
X-Ray Microtomography
Bone and Bones immunology
Bone and Bones metabolism
Complement Factor H immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3279
- Volume :
- 223
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Immunobiology
- Publication Type :
- Academic Journal
- Accession number :
- 30107932
- Full Text :
- https://doi.org/10.1016/j.imbio.2018.07.023