Modulation of rabbit articular chondrocyte (RAC) proliferation by TGF-beta isoforms.
We have previously shown that TGF-beta 1 exerts a bifunctional effect on RAC proliferation. Added to quiescent cultures, it inhibits the entry of G0/G1 cells into S phase whereas in S phase synchronized populations, it stimulates the DNA replication rate with a delayed G2 + M phase and a subsequent transient increase of cell number. As TGF-beta 2 and beta 3 isoforms are also expressed in bone and cartilage tissues, it was of interest to study their effect on RAC proliferation, in comparison to that of TGF-beta 1. Using cell counting and tritiated thymidine incorporation, we found that all the TGF-beta s used here induced an increase of RAC proliferation rate occurring between 24 and 48 h of exposure. TGF-beta 2 appeared as the most efficient form as judged from the maximum of thymidine labelling. However, TGF-beta 3 induced an increase of cell number slightly higher than both TGF-beta 1 and TGF-beta 2 (+30% versus 20% for TGF-beta 1 and beta 2). TGF-beta 2 and beta 3 were able to stimulate the DNA replication rate as previously demonstrated for TGF-beta 1. However, the effect occurred later for TGF-beta 2 and beta 3 (12 h) than for TGF-beta 1 (6 h). This was confirmed by flow cytometric analysis of DNA content. In addition, immunodetection by flow cytometry demonstrated that all TGF-beta isoforms enhanced endogenous expression of TGF-beta-related peptides. The effect was shown to be associated with the cell cycle S phase and was greater for TGF-beta 3 than for TGF-beta 1 and beta 2. These findings suggest that TGF-beta s could act on RAC functions via autocrine and paracrine ways. Taken together, these data indicate that TGF-beta s may modulate proliferation of articular chondrocytes and therefore could play a role in the activation of these cells in the early stages of osteoarthritis.
Boumediene
K
K
Laboratoire de Biochimie du Tissu Conjonctif CJF INSERM Caen, France.
Vivien
D
D
Macro
M
M
Bogdanowicz
P
P
Lebrun
E
E
Pujol
J P
JP
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology* / Q000187:drug effects; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D011817:Rabbits; D013936:Thymidine; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*; D014316:Tritium
D016212:Transforming Growth Factor beta; D014316:Tritium; D013936:Thymidine