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 neonatal rat calvariae. Cells were cultured for 72 h on Coll-I gel matrix and compared with control cells plated on plastic surfaces. Agonist-dependent 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 UMR-106 cells, the collagen matrix effect was mimicked by 24-h incubation with soluble Coll-I or short peptides containing the arginine-glycine-aspartate motif. Accumulation of cellular adenosine 3',5'-cyclic monophosphate (cAMP) stimulated by parathyroid hormone, cholera toxin, and forskolin was augmented (50-150%) in cells plated on Coll-I vs. control. The collagen effect on both [Ca2+]i- and adenylate cyclase-signaling pathways in UMR-106 cells was abrogated in the presence of protein kinase C (PKC) depletion or inhibition. Also, Coll-I induced a twofold increase in membrane-bound PKC without changing cytosolic PKC activity. Thus, by altering PKC activity, Coll-I modulates the [Ca2+]i- and cAMP-signaling pathways in osteoblasts. This, in turn, may influence bone remodeling processes.
Green
J
J
Department of Medicine, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, University of California, School of Medicine, Los Angeles 90048, USA.
Schotland
S
S
Stauber
D J
DJ
Kleeman
C R
CR
Clemens
T L
TL
D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology / Q000502:physiology*; D000242:Cyclic AMP / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology*; D009994:Osmolar Concentration; D010006:Osteoblasts / Q000502:physiology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D010455:Peptides; D003094:Collagen; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium