Inflammatory cytokines induce a unique mineralizing phenotype in mesenchymal stem cells derived from human bone marrow.

摘要: Bone marrow contains mesenchymal stem cells (MSCs) that can differentiate along multiple lineages. In this capacity they are thought to be important in the intrinsic turnover and repair of connective tissues while also serving as a basis for tissue engineering regenerative medicine. However, little is known biological responses human MSCs inflammatory conditions. When cultured with IL-1β, marrow-derived from 8 10 subjects deposited copious hydroxyapatite, which authenticity was confirmed by Fourier transform infrared spectroscopy. Transmission electron microscopy revealed production fine needles hydroxyapatite conjunction matrix vesicles. Alkaline phosphatase activity did not increase response mediators, but PPi fell, reflecting lower ectonucleotide pyrophosphatase Because major physiological inhibitor mineralization, its decline generated permissive conditions formation. This contrast treated dexamethasone, where levels fall mineralization fuelled large rapid alkaline activity. sialoprotein only osteoblast marker strongly induced IL-1β; thus these do become osteoblasts despite depositing abundant mineral. RT-PCR detect transcripts indicative alternative lineages, including chondrocytes, myoblasts, adipocytes, ligament, tendon, or vascular smooth muscle cells. IL-1β phosphorylated MAPKs activated nuclear factor-κB (NF-κB). Certain inhibitors MAPK PI3K, NF-κB, prevented mineralization. The findings importance soft engineering,