CELL-MATRIX INTERACTION IN BONE - TYPE-I COLLAGEN MODULATES SIGNAL-TRANSDUCTION IN OSTEOBLAST-LIKE CELLS

Cell interaction with extracellular matrix (ECM) modulates cell growth and differentiation. By using in vitro culture systems, we tested the effect of type I collagen (Coll-I) on signal transduction mechanisms in the osteosarcoma cell line UMR-106 and in primary cultures from neo natal rat calvariae. Cells were cultured for 72 h on Coll-I gel matrix and compared with control cells plated on plastic surfaces. Agonist-d ependent and voltage-dependent rises in cytosolic Ca2+ concentration ( [Ca2+](i); measured by fura 2 fluorometry) were significantly blunted in cells cultured on Coll-I compared with cells grown on plastic. In U MR-106 cells, the collagen matrix effect was mimicked by 24-h incubati on with soluble Coll-I or short peptides containing the arginine-glyci ne-aspartate motif. Accumulation of cellular adenosine 3',5'-cyclic mo nophosphate (cAMP) stimulated by parathyroid hormone, cholera toxin, a nd forskolin was augmented (50-150%) in cells plated on Coll-I vs. con trol. The collagen effect on both [Ca2+](i)- and adenylate cyclase-sig naling pathways in UMR-106 cells was abrogated in the presence of prot ein kinase C (PKC) depletion or inhibition. Also, Coll-I induced a two fold increase in membrane-bound PKC without changing cytosolic PKC act ivity. Thus, by altering PKC activity, Coll-I modulates the [Ca2+](i)- and cAMP-signaling pathways in osteoblasts. This, in turn, may influe nce bone remodeling processes.