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Am J Physiol Cell Physiol. 2016 Oct 1;311(4):C673-C685. doi: 10.1152/ajpcell.00331.2015. Epub 2016 Aug 3.

Deletion of calponin 2 in macrophages attenuates the severity of inflammatory arthritis in mice.

Author information

1
Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and.
2
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan.
3
Department of Pathology, University of Rochester, Rochester, New York.
4
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan; jjin@med.wayne.edu.

Abstract

Calponin is an actin cytoskeleton-associated protein that regulates motility-based cellular functions. Three isoforms of calponin are present in vertebrates, among which calponin 2 encoded by the Cnn2 gene is expressed in multiple types of cells, including blood cells from the myeloid lineage. Our previous studies demonstrated that macrophages from Cnn2 knockout (KO) mice exhibit increased migration and phagocytosis. Intrigued by an observation that monocytes and macrophages from patients with rheumatoid arthritis had increased calponin 2, we investigated anti-glucose-6-phosphate isomerase serum-induced arthritis in Cnn2-KO mice for the effect of calponin 2 deletion on the pathogenesis and pathology of inflammatory arthritis. The results showed that the development of arthritis was attenuated in systemic Cnn2-KO mice with significantly reduced inflammation and bone erosion than that in age- and stain background-matched C57BL/6 wild-type mice. In vitro differentiation of calponin 2-null mouse bone marrow cells produced fewer osteoclasts with decreased bone resorption. The attenuation of inflammatory arthritis was confirmed in conditional myeloid cell-specific Cnn2-KO mice. The increased phagocytotic activity of calponin 2-null macrophages may facilitate the clearance of autoimmune complexes and the resolution of inflammation, whereas the decreased substrate adhesion may reduce osteoclastogenesis and bone resorption. The data suggest that calponin 2 regulation of cytoskeleton function plays a novel role in the pathogenesis of inflammatory arthritis, implicating a potentially therapeutic target.

KEYWORDS:

calponin 2; cell adhesion; inflammatory arthritis; macrophages; osteoclasts

PMID:
27488671
PMCID:
PMC5129749
DOI:
10.1152/ajpcell.00331.2015
[Indexed for MEDLINE]
Free PMC Article

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