Two different isoforms of osteopontin modulate myelination and axonal integrity

Abnormal myelination underlies the pathology of white matter diseases such as preterm injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into secreted isoform (sOPN) or an intracellular (iOPN). Whether there isoform-specific involvement unknown. Here we generated mouse models that either lacked both isoforms all cells (OPN-KO) sOPN systemically but expressed iOPN specifically oligodendrocytes (OLs-iOPN-KI). Transcriptome analysis isolated from neonatal brain showed genes pathways related increase altered cell cycle control were enriched absence two OPN-KO mice compared mice. Accordingly, adult increased axonal myelination, revealed by transmission electron microscopy imaging, expression myelin-related proteins. In contrast, OLs-iOPN-KI differential regulation adhesion, motility, vasculature development, decrease axonal/neuronal development. abnormal myelin formation early phase young signs degeneration adulthood. These results suggest involvement, possible interplay between isoforms, integrity. Thus, need be separately considered therapeutic strategies targeting diseases.