The Role of Myo/Nog Cells During the Pathogenesis of Rheumatoid Arthritis
Date of Award
5-2018
Degree Type
Thesis
Degree Name
Master of Science in Biomedical Sciences
First Advisor
Rangaiah Shashidharamurthy, PhD
Second Advisor
Bonnie Buxton, PhD
Third Advisor
Richard White, PhD, FAHA
Fourth Advisor
Srujana Rayalam, BVSc, MVSc, PhD
Abstract
Arthritis is a debilitating disease that affects all aspects of life. Autoimmune diseases, like rheumatoid arthritis, are often aggravated by the involvement of innate and adaptive immune cells. Mesenchymal cell involvement during the progression of RA has been observed in recent studies. Noggin-secreting mesenchymal cells, Myo/Nog cells, are observed in the epiblast of chick embryos, are recruited to wound sites in the skin, and are neuroprotective in retinal disorders. However, the role of Myo/Nog cells in chronic inflammatory conditions has yet to be elucidated. Here, we have shown that G8 antigen positive Myo/Nog cells localize at the arthritic joints using murine models of collagen antibody induced arthritis (CAIA). Noggin is an established inhibitor of the bone morphogenetic protein (BMP) signaling pathway, which have been observed to mediate inflammation during autoimmune arthritis. Our results show the secretion of Noggin by Myo/Nog cells when stimulated by pro-inflammatory cytokines, indicating that Noggin might be the means by which Myo/Nog cells exert their action by inhibiting the pathogenic BMP-mediated signaling pathway. In addition, lipocalin2 knockout (Lcn2KO) mice exhibited exacerbated arthritic condition with increased secretion of IL-6 and IL-1 p than their wild type (WT) littermates with increased extravasation of G8+ cells at the arthritic joint. Collectively, our data suggests that Lcn2 is required for the recruitment of Myo/Nog cells at the site of inflammation, and that these cells protect the joint from severe degeneration by inhibiting the pathogenic BMP signaling pathway through the secretion of Noggin.
Recommended Citation
López Garcia, María J., "The Role of Myo/Nog Cells During the Pathogenesis of Rheumatoid Arthritis" (2018). PCOM Biomedical Studies Student Scholarship. 149.
https://digitalcommons.pcom.edu/biomed/149