Growth factor regulation of smooth muscle actin expression and contraction of human articular chondrocytes and meniscal cells in a collagen-GAG matrix.
Recent work has demonstrated that human articular chondrocytes and meniscus cells can express the gene for a contractile actin isoform, alpha-smooth muscle actin (SMA), in vivo. The objective of the present study was to evaluate the effects of two growth factors, transforming growth factor (TGF)-beta1 and platelet-derived growth factor (PDGF)-BB, on the SMA content of these cells and their contraction of a collagen-glycosaminoglycan (GAG) analog of extracellular matrix in vitro. TGF-beta1 was found to markedly increase SMA content of the cells and PDGF-BB decreased SMA expression, with both findings achieving statistical significance. A notable finding was the increased contraction of the collagen-GAG matrix induced by TGF-beta1 and the decrease in contraction resulting from PDGF-BB treatment, indicating a causal relationship between expression of SMA and the contractility of the cells. A novel cell force monitor, employed to estimate the force exerted per cell, demonstrated a higher force exerted by the TGF-beta1-treated cells. The findings demonstrate that the expression of SMA by articular chondrocytes and meniscal cells and their associated contractile behavior can be regulated by selected growth factors. This work provides a foundation for the rational investigation of the mechanisms underlying SMA-enabled contraction of these cell types and the control of this behavior in tissue engineering.
Zaleskas
J M
JM
Department of Orthopaedic Surgery, MRB 106, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
Kinner
B
B
Freyman
T M
TM
Yannas
I V
IV
Gibson
L J
LJ
Spector
M
M
D000199:Actins / Q000096:biosynthesis*; D000328:Adult; D000077214:Becaplermin; D015153:Blotting, Western / Q000379:methods; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D008592:Menisci, Tibial / Q000166:cytology / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D000199:Actins; D006025:Glycosaminoglycans; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin; D003094:Collagen