Retinoic acid effects on an SV-40 large T antigen immortalized adult rat bone cell line

J Cell Physiol. 1999 Jun;179(3):267-75. doi: 10.1002/(SICI)1097-4652(199906)179:3<267::AID-JCP4>3.0.CO;2-0.

Abstract

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.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Antigens, Polyomavirus Transforming*
  • Antineoplastic Agents / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Division / drug effects
  • Cell Line, Transformed / drug effects
  • Cell Survival / drug effects
  • Collagen / genetics
  • Culture Media, Conditioned / pharmacology
  • Drug Synergism
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism
  • Female
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Integrin alpha1beta1
  • Integrins / analysis
  • Integrins / genetics
  • Osteocytes / cytology*
  • Osteocytes / drug effects*
  • Osteocytes / enzymology
  • RNA, Messenger / analysis
  • Rats
  • Tibia / cytology
  • Tretinoin / pharmacology*

Substances

  • Antigens, Polyomavirus Transforming
  • Antineoplastic Agents
  • Culture Media, Conditioned
  • Integrin alpha1beta1
  • Integrins
  • RNA, Messenger
  • Fibroblast Growth Factor 2
  • Tretinoin
  • Collagen
  • Alkaline Phosphatase