Retinoic acid effects on an SV-40 large T antigen immortalized adult rat bone cell line.
Clonal cell lines were established from adult rat tibia cells immortalized with SV-40 large T antigen. One clone (TRAB-11), in which retinoic acid (RA) induced alkaline phosphatase (AP) activity, was selected for further study. The TRAB-11 cells express high levels of type I collagen mRNA, type IV collagen, fibronectin, practically no type III collagen, little osteopontin, and no osteocalcin. RA stimulates proliferation of TRAB-11 cells (starting at 10 pM) and survival (starting at 100 pM). TRAB-11 cells synthesize fibroblast growth factor-2 (FGF-2), which has potent autocrine mitogenic effects on these cells and acts synergistically with RA. TRAB-11 cells attach better to type IV collagen than to fibronectin or laminin. Cell attachment to type IV collagen is increased by RA and decreased (65%) by an antibody directed against alpha1beta1 integrin. RA up-regulates steady-state levels of alpha1, mRNA without affecting beta1 mRNA expression. In conclusion, we report the establishment of a clonal cell line from the outgrowth of adult rat tibiae which is highly sensitive to RA in its growth and survival in culture, apparently as a result of integrin-mediated cell interaction with extracellular matrix proteins.
Lafage-Proust
M H
MH
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Wesolowski
G
G
Ernst
M
M
Rodan
G A
GA
Rodan
S B
SB
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004357:Drug Synergism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D039222:Integrin alpha1beta1; D016023:Integrins / Q000032:analysis / Q000235:genetics; D010011:Osteocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013977:Tibia / Q000166:cytology; D014212:Tretinoin / Q000494:pharmacology*
D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D039222:Integrin alpha1beta1; D016023:Integrins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D014212:Tretinoin; D003094:Collagen; D000469:Alkaline Phosphatase