PMID- 8253864
OWN - NLM
STAT- MEDLINE
DCOM- 19940113
LR  - 20131121
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 157
IP  - 3
DP  - 1993 Dec
TI  - Plasminogen-dependent activation of latent transforming growth factor beta (TGF 
      beta) by growing cultures of osteoblast-like cells.
PG  - 528-34
AB  - Osteoblasts secrete transforming growth factor beta (TGF beta) as a biologically 
      inert, latent complex that must be dissociated before the growth factor can exert 
      its effects. We have examined the production and proteolytic activation of latent 
      TGF beta (LTGF beta) by clonal UMR 106-01 rat osteosarcoma cells and neonatal 
      mouse calvarial (MC) osteoblast-like cells in vitro. Synthetic bPTH-(1-34) 
      increased the activity of tissue-type (tPA) and urokinase-type (uPA) plasminogen 
      activators (PA) in cell lysates (CL) of UMR 106-01 cells. The concentration of 
      active TGF beta in serum-free CM from cultures treated with bPTH-(1-34) and 
      plasminogen was significantly greater than in CM from untreated controls and 
      cultures treated with either bPTH-(1-34) or plasminogen alone. This effect 
      occurred at concentrations of PTH-(1-34) that increased PA activity and was 
      prevented by aprotinin, an inhibitor of plasmin activity. Treatment with 
      bPTH-(1-34) had no effect on the concentration of TGF beta in acid-activated 
      samples of CM. Functional consequences of proteolytically activated TGF beta was 
      examined in primary cultures of neonatal MC osteoblast-like cells. Human platelet 
      TGF beta 1 caused a dose-dependent increase in the migration of these cells in an 
      in vitro wound healing assay. Cell migration was also stimulated in cultures 
      treated with bPTH-(1-34) and plasminogen together. This effect was blocked by an 
      anti-TGF beta 1 antibody. The results of these studies demonstrate that (1) LTGF 
      beta secreted by osteoblasts in vitro is activated under conditions where the 
      plasmin activity in the cultures is increased, and (2) the TGF beta generated by 
      plasmin-mediated proteolysis is biologically active. We suggest that the local 
      concentration of TGF beta in bone may be controlled by the osteoblast-associated 
      plasminogen activator/plasmin system. Furthermore, since several calciotropic 
      factors influence osteoblast PA activity, this system may have an important role 
      in mediating their anabolic and/or catabolic effects.
FAU - Yee, J A
AU  - Yee JA
AD  - Department of Biomedical Sciences, Creighton University, School of Medicine, 
      Omaha, NE 68178.
FAU - Yan, L
AU  - Yan L
FAU - Dominguez, J C
AU  - Dominguez JC
FAU - Allan, E H
AU  - Allan EH
FAU - Martin, T J
AU  - Martin TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Peptide Fragments)
RN  - 0 (Transforming Growth Factor beta)
RN  - 10T9CSU89I (Teriparatide)
RN  - 9001-91-6 (Plasminogen)
RN  - EC 3.4.21.- (Plasminogen Activators)
SB  - IM
MH  - Animals
MH  - Blood Platelets/metabolism
MH  - Cattle
MH  - Cell Division
MH  - Cell Movement
MH  - Humans
MH  - Mice
MH  - Osteoblasts/cytology/*metabolism
MH  - Parathyroid Hormone/pharmacology/physiology
MH  - Peptide Fragments/pharmacology
MH  - Plasminogen/*physiology
MH  - Plasminogen Activators/pharmacology
MH  - Rats
MH  - Teriparatide
MH  - Transforming Growth Factor beta/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 1993/12/01 00:00
MHDA- 1993/12/01 00:01
CRDT- 1993/12/01 00:00
PHST- 1993/12/01 00:00 [pubmed]
PHST- 1993/12/01 00:01 [medline]
PHST- 1993/12/01 00:00 [entrez]
AID - 10.1002/jcp.1041570312 [doi]
PST - ppublish
SO  - J Cell Physiol. 1993 Dec;157(3):528-34. doi: 10.1002/jcp.1041570312.