Type I collagen substrate increases calcitonin and parathyroid hormone receptor-mediated signal transduction in UMR 106-06 osteoblast-like cells.
Components of the extracellular matrices (ECM) exert pleiotropic effects in many cell systems, but little is known of the effect of ECM on hormone signal transduction. We have investigated the effect of ECM substrates on cell growth and signal transduction by calcitonin (CT) and parathyroid hormone (PTH) using the rat osteosarcoma cell line, UMR 106-06. Type I collagen (collagen[I]) and Matrigel changed the morphology of the cells and significantly inhibited cell growth by 37% or 23%, respectively, compared with control. None of laminin, fibronectin, or type IV collagen affected cell shape or proliferation. Cells cultured on collagen (I)-coated plates showed increased specific binding of labeled CT compared with cells on plastic plates. The effect was apparent by 24 h and persisted for at least 72 h. None of the other ECM affected CT binding. Scatchard analysis revealed that collagen(I) increased CT receptor numbers but not receptor affinity. Consistent with increased binding capacity, cells plated on collagen(I) had increased responses to each of CT and PTH in terms of cyclic adenosine monophosphate (cAMP) production compared to control cells. In addition, cAMP production by prostaglandin E2, cholera toxin, and forskolin was increased by 30-70% compared to control. These data suggest that collagen(I) had effects not only on membrane receptors but on guanosine triphosphate (GTP) binding proteins (G proteins). The effect of collagen(I) on CT binding was no longer present when the cells were freed from the plates by enzymatic dispersion and binding measured in cell suspensions. In UMR 106-01 cells transiently transfected with the porcine CT receptor cDNA, binding was similarly induced by collagen(I). These data are the first demonstration that collagen(I) may play an important role in signal transduction, affecting both receptors and G proteins in UMR 106-06 cells. These results draw attention to the potential role of the ECM of bone in hormone-induced responses.
Ikeda
K
K
St. Vincent's Institute of Medical Research, Melbourne, Victoria, Australia.
Michelangeli
V P
VP
Martin
T J
TJ
Findlay
D M
DM
D000818:Animals; D002455:Cell Division; D003094:Collagen / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D010006:Osteoblasts / Q000502:physiology*; D051381:Rats; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000502:physiology*; D018016:Receptors, Parathyroid Hormone; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D003094:Collagen; D000242:Cyclic AMP