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 pro alpha 1 (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.
Seitzer
U
U
Institut für Medizinische Molekularbiologie, Medizinische Universität zu Lübeck, Germany.
Bätge
B
B
Acil
Y
Y
Müller
P K
PK
D000328:Adult; D015152:Blotting, Northern; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism*; D015342:DNA Probes; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D006900:Hydroxylation; D006901:Hydroxylysine / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010013:Osteogenesis Imperfecta / Q000378:metabolism; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000096:biosynthesis* / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D015342:DNA Probes; D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D006901:Hydroxylysine; D003094:Collagen; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D008239:Lysine