Transforming growth factor beta(1) influences lysyl hydroxylation of collagen I and reduces steady-state levels of lysyl hydroxylase mRNA in human osteoblast-like cells

Transforming growth factor beta(1) (TGF-beta(1)) is an osteotropic growth factor that is found in substantial concentration in bone. The authors studied the influence of TGF-beta(1) on the modification of lysine residues of collagen I. The degree of lysyl hydroxylation and lysyl glycosylation of newly synthesized collagen as well as steady-state levels of mRNA for both lysyl hydroxylase and collagens I and III were determined in human osteoblast-like cells in vitro. In normal human osteoblasts lysyl hydroxylation was decreased by TGF-beta(1) particularly in the collagen alpha(2)-chain. This effect was paralleled by an increase in lysyl residues, whereas glycosylation was not affected. The mRNA for lysyl hydroxylase was reduced by one-third under the influence of TGF-beta(1). Additionally, the mRNAs for both procollagen I alpha-chains were stimulated by TGF-beta(1), whereas proal(III)-mRNA showed a decrease. Changes in the local regulatory activity of TGF-beta(1) may play a role in matrix maturation such as collagen type production and lysyl hydroxylation, the latter being altered in various pathological conditions, e.g. in generalized osteopenia.