University of Zagreb. School of Medicine. Department of Anatomy and Clinical Anatomy.
Abstract
Reumatoidni artritis (RA) je kronična sustavna autoimunosna bolest karakterizirana osteodestruktivnom upalom malih zglobova šake i stopala i posljedičnom invalidnošću bolesnika. Artritis potaknut antigenom (AIA) smatra se zglobno ograničenim mišjim modelom RA, bez sustavnih učinaka. Budući da model uključuje imunizaciju uz korištenje Freundovog adjuvansa, za koji je opisano postojanje sustavnih učinaka na stanice imunosnog sustava, primarni cilj našeg istraživanja bio je utvrditi jakost tih učinaka u modelu AIA te razvija li se u okviru tog modela generalizirana osteopenija. Miševi su podijeljeni u tri skupine: neimuniziranu skupinu, kontrolnu imuniziranu skupinu te skupinu miševa s artritisom. Volumen koštanih gredica procijenjen je mikro-kompjutoriziranom tomografijom u lumbalnim kralješcima te u femoralnim metafizama i epifizama. Pokazatelj učinka na stanice imunosnog sustava bio je udio mijeloidnih (CD11b+Gr1+) stanica u slezeni, femoralnoj koštanoj srži te koljenom zglobu, određen protočnom citometrijom. Rezultati su potvrdili da imunizacija u okviru AIA izaziva sustavni upalni odgovor koji se očituje povećanjem udjela mijeloidnih stanica u slezeni i koštanoj srži te generaliziranu osteopeniju, koja najjače pogađa koštane gredice femoralnih metafiza. Lokalno nakupljanje mijeloidnih stanica i gubitak epifiznih koštanih gredica najjače su potaknuti artritisom. Budući da je učinak imunizacije na epifizne koštane gredice minimalan, mjerenje u tom području je najpouzdaniji pokazatelj lokalnih koštanih učinaka artritisa.Rheumatoid arthritis (RA) is a systemic autoimmune disease marked by osteodestructive inflammation of joints of hands and feet and progressive disability. Antigen-induced arthritis (AIA) is considered as a localized murine model of RA, lacking systemic effects. Immunization protocol in AIA applies Freund’s adjuvant, with well documented systemic effects on the cells of the immune system. Therefore, primary goal of our study was to determine intensity of systemic effects, especially the development of generalized osteopenia. Mice were divided in three groups: non-immunized, immunized control, and a group with arthritis. Trabecular bone was measured using micro-computed tomography, in the second lumbar vertebrae, femoral metaphyses and epiphyses. To determine systemic, immune-related effect, proportion of myeloid (CD11b+Gr1+) cells was assessed by flow cytometry in the spleen, femoral bone marrow and knees. Results indicate that immunization protocol in AIA induces systemic increase in proportion of myeloid cells accompanied by generalized bone loss, most prominent in femoral metaphyseal trabeculae. Significant accumulation of myeloid cells in knees affected by arthritis is accompanied by a loss of epiphyseal trabeculae. As immunization has a minimal effect on the epiphyseal trabecular bone, femoral epiphyses are the most reliable region for the quantitative assessment of the local osteodestructive effect of arthritis
