The effects of age on rabbit MCL fibroblast matrix synthesis in response to TGF-beta 1 or EGF.
In this study, we examined the effects of age on collagen and total protein synthesis by ligament fibroblasts in response to growth factors. Three different doses of transforming growth factor-beta 1 (TGF-beta 1) or epidermal growth factor (EGF) were individually added to in vitro fibroblast cultures from the medial collateral ligament (MCL) of skeletally immature (age 3 months), mature (age 12 months) and senescent (age 48-51 months) rabbits. Analysis of the effects of age revealed that fibroblasts from senescent rabbits produced significantly less collagen in response to TGF-beta 1 or EGF stimulation when compared to fibroblasts from immature rabbits. Furthermore, increased age was found to result in significant reductions in the baseline levels of collagen synthesis but not total protein synthesis. Additionally, collagen and total protein synthesis by MCL fibroblasts were significantly affected by the TFG-beta 1 dose, but not by the EGF dose. When fibroblasts were normalized to their own controls, the increase in collagen and total protein synthesis due to TGF-beta 1 and EGF for the senescent group were found to be greater than those for the skeletally immature rabbits at all doses. This demonstrates that MCL fibroblasts from senescent rabbits are responsive to growth factors.
Deie
M
M
Department of Orthopaedic Surgery, University of Pittsburgh, PA 15213, USA.
Marui
T
T
Allen
C R
CR
Hildebrand
K A
KA
Georgescu
H I
HI
Niyibizi
C
C
Woo
S L
SL
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017888:Medial Collateral Ligament, Knee / Q000166:cytology; D014176:Protein Biosynthesis; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D003094:Collagen