Expression of extracellular matrix genes: Transforming growth factor (TGF)-beta 1 and ras in tibial fracture healing of lathyritic rats

Experimental osteolathyrism, induced by dietary aminoacetonitrile (AAN), wa s used to study the effect of altered extracellular matrix on the expressio n of connective tissue components in long bone healing, AAN inhibits lysyl oxidase, which is needed for the formation of collagen cross-link precursor s, and is also shown to act as a regulator of Ras, Fractured tibias in lath yritic rats develop excessive amounts of mechanically weak callus tissue wi th irregular cartilage and reduced glycosaminoglycan accumulation, Cartilag e-specific proteins (collagen types II, IX, and X and aggrecan) were expres sed temporally much wider in lathyritic calluses than in the controls, and active transcription was observed even during the fibrous and ossifying sta ges. Soft connective tissue was still present in 2- and 3-week-old lathyrit ic calluses and could explain the elevated type III collagen, biglycan, and decorin mRNA levels. Both transforming growth factor (TGF)-beta 1 and c-Ha -ras, which control cell growth and differentiation, were upregulated durin g the cartilaginous stage, The maximal expression of TGF-beta 1 preceded th at of ras in osteolathyrism, (Bone 27:551-557; 2000) (C) 2000 by Elsevier S cience Inc, All rights reserved.