LEUKEMIA INHIBITORY FACTOR AND ONCOSTATIN-M INFLUENCE THE MINERAL PHASES FORMED IN A MURINE HETEROTOPIC CALCIFICATION MODEL - A FOURIER-TRANSFORM INFRARED MICROSPECTROSCOPIC STUDY

The study of bone mineralization processes is of considerable interest in understanding bone diseases and developing new therapies for skele tal disorders, particularly since bone homeostasis requires numerous c ell types and a large cytokine network Cell culture models of minerali zation have often been used to study the cellular mechanisms of minera lization, but few data have been reported concerning the influence of extracellular matrix components and cytokines on the physicochemical p roperties of mineral. The purpose of this study was to analyze the eff ects of two cytokines, leukemia inhibitory factor (LIF) and oncostatin M (OSM), involved in bone metabolism on the physicochemical propertie s of bone mineral formed in a murine in vivo mineralization model. Mur ine bone marrow cells implanted under the kidney capsule in the presen ce or absence of cytokines led to heterotopic ossicle formation. A sca nning electron microscopic microprobe revealed that heterotopic calcif ication had a lower (similar to 20%) Ca/P ratio after cytokine treatme nt as compared with the control without cytokine, Transmission electro n microscopic analysis of cytokine-treated ossicles showed numerous ar eas with low mineral density, whereas electron diffraction pattern rev ealed an apatitic phase. These areas were not observed in the absence of cytokine, Moreover, Fourier transform-infrared microspectroscopy sh owed at the molecular level that the presence of either cytokine induc ed many microscopic areas in which short-range order organization, suc h as incorporation of carbonate and crystallinity/maturity of ossicle mineral, were modified. LIF and OSM influenced mineral phase formation in the present model and may thus be key protagonists in bone mineral development and skeletal diseases.