Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Deletion of calponin 2 in macrophages attenuates the severity of inflammatory arthritis in mice. 2748 71

Calponin 2 is an actin cytoskeleton-associated regulatory protein that inhibits the activity of myosin-ATPase and cytoskeleton dynamics. Recent studies have demonstrated that deletion of calponin 2 restricts the proinflammatory activation of macrophages in atherosclerosis and arthritis to attenuate the disease progression in mice. Here we demonstrate that the levels of calponin 2 vary among different macrophage populations, which may reflect their adaptation to specific tissue microenvironment corresponding to specific functional states. Interestingly, lung resident macrophages express significantly lower calponin 2 than peritoneal resident macrophages, which correlates with decreased substrate adhesion and reduced expression of proinflammatory cytokines and a proresolution phenotype. Deletion of calponin 2 in peritoneal macrophages also decreased substrate adhesion and downregulated the expression of proinflammatory cytokines. Providing the first line of defense against microbial invasion while receiving constant exposure to extrinsic antigens, lung macrophages need to maintain a necessary level of activity while limiting exaggerated inflammatory reaction. Therefore, their low level of calponin 2 may reflect an important physiological adaption. Downregulation of calponin 2 in macrophages may be targeted as a cytoskeleton-based novel mechanism, possibly via endoplasmic reticulum stress altering the processing and secretion of cytokines, to regulate immune response and promote quiescence for the treatment of inflammatory diseases.
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PMID:Downregulation of calponin 2 contributes to the quiescence of lung macrophages. 3136 93

While the rapid development of CRISPR/CAS9 technology has allowed for readily performing site-specific genomic editing in non-rodent species, an emerging challenge is to select the most suitable species to generate animal models for the study of human biology and diseases. Improving CRISPR/CAS9 methodology for more effective and precise editing in the rabbit genome to replicate human disease is an active area of biomedical research. Although rabbits are more closely related to humans than mice (based on DNA sequence analysis), our whole-genome protein database search revealed that rabbits have more missing human protein sequences than mice. Hence, precisely replicating human diseases in rabbits requires further consideration, especially in studies involving essential functions of the missing proteins. For example, rabbits lack calponin 2, an actin-associated cytoskeletal protein that is important in the pathogenesis of inflammatory arthritis, atherosclerosis, and calcific aortic valve disease. The justification of using rabbits as models for human biomedical research is based on their larger size and their closer phylogenetic distance to humans (based on sequence similarity of conserved genes), but this may be misleading. Our findings, which consider whole-genome protein profiling together with actual protein expressions, serve as a warning to the scientific community to consider overall conservation as well as the conservation of specific proteins when choosing an animal model to study a particular aspect of human biology prior to investing in genetic engineering.
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PMID:The Absence of Calponin 2 in Rabbits Suggests Caution in Choosing Animal Models. 3218 66