M. Le et al., Transglutaminase participates in the incorporation of latent TGF beta intothe extracellular matrix of aging articular chondrocytes, CONNECT TIS, 42(4), 2001, pp. 245
TGF beta1 is a multifunctional peptide growth factor that promotes processe
s associated with age-related degenerative diseases in articular cartilage.
Large quantities of TGF beta1 are stored in cartilage extracellular matrix
(ECM) in a latent form (LTGF beta1), and yet little is known about the fac
tors that participate in the incorporation of LTGF beta1 into the highly sp
ecialized cartilage ECM. We previously demonstrated high levels of the prot
ein cross-linking enzyme transglutaminase (TGase) in aging articular chondr
ocytes and showed that this enzyme participated in LTGF beta1 activation. T
his work explores the hypothesis that extracellular TGase participates in L
TGF beta1 incorporation into ECM in aging chondrocytes. We studied the effe
cts of TGase inhibitors on TGF beta1 levels in ECM of old and young porcine
articular chondrocytes. TGase inhibitors decreased the quantity of LTGF be
ta1 in the ECM in old but not in young chondrocytes to 60-70% of control va
lues (p < .05). Fibronectin, an extracellular TGase competitive substrate,
also decreased LTGF beta1 levels in ECM (p < .01). Levels of activated TGF
beta1 also decreased in the presence of TGase inhibitors, as did levels of
latent TGF beta binding protein I in the cell layer. Extracellular TGase ac
tivity was present in old but not young chondrocyte cultures. These finding
s support a role for extracellular TGase in the incorporation of LTGF beta1
in the ECM of aging chondrocytes.