Avidin expression during chick chondrocyte and myoblast development in vitro and in vivo: regulation of cell proliferation

Avidin is a major [S-35]methionine-labeled protein induced by bacterial lip opolysaccharide (LPS) and interleukin 6 (IL-6) in cultured chick embryo myo blasts and chondrocytes, It was identified by N-terminal sequencing of the protein purified from conditioned culture medium of LPS-stimulated myoblast s, In addition, avidin was secreted by unstimulated myoblasts and chondrocy tes during in vitro differentiation; maximal expression being observed in d ifferentiated myofibers and hypertrophic chondrocytes. In developing chick embryos, immunohistochemistry revealed avidin in skeletal muscles and growt h plate hypertrophic cartilage. Avidin was secreted into culture as a biolo gically active tetramer, Exogenous avidin added to the medium of proliferat ing chondrocytes progressively inhibited cell proliferation, whereas additi on of avidin to differentiating chondrocytes in suspension allowed full cel l differentiation. No toxic effects for the cells were observed in both cul ture conditions. Western blots of samples from cytosolic extracts using alk aline-phosphatase-conjugated streptavidin showed three biotin-containing pr oteins. Acetyl-CoA carboxylase was identified by specific antibodies. Based on these data, we propose that avidin binds extracellular biotin and regul ates cell proliferation by interfering with fatty acid biosynthesis during terminal cell differentiation and/or in response to inflammatory stimuli.