title: Deletion of calponin 2 in macrophages attenuates the severity of inflammatory arthritis in mice.
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.
authors.affiliation: Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and.
authors.forename: Qi-Quan
authors.initials: QQ
authors.lastname: Huang
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: M Moazzem
authors.initials: MM
authors.lastname: Hossain
authors.affiliation: Department of Pathology, University of Rochester, Rochester, New York.
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pathology, University of Rochester, Rochester, New York.
authors.forename: Lianping
authors.initials: L
authors.lastname: Xing
authors.affiliation: Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Pope
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan; jjin@med.wayne.edu.
authors.forename: J-P
authors.initials: JP
authors.lastname: Jin
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics / Q000502:physiology; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D005956:Glucose-6-Phosphate Isomerase; D008840:Microfilament Proteins; D000096985:Calponins
keywords: calponin 2; cell adhesion; inflammatory arthritis; macrophages; osteoclasts