Differential effect of flavonoids on glycosaminoglycan content and distribution in skin fibroblasts of patients with type I osteogenesis imperfecta

We recently reported that, in osteogenesis imperfecta (OI) type I with diminished type I collagen biosynthesis, flavonoids such as apigenin 7-O-glucuronide, apigenin 7-O-methylglucuronide and pectolinarin normalized the level of collagen type I without affecting total protein synthesis. In addition to collagen, glycosaminoglycans (GAGs) play an important role in the formation of a functional supramolecular complex in the extracellular matrix, and any changes in their content and/or composition may be involved in the OI phenotype. We previously detected a marked increase in sulphated GAG content in the OI fibroblasts of more severely affected patients (OI types II and III). These alterations were more pronounced in medium than in cells. Although, in OI type I cells, the increase observed in medium was much smaller (approximately 1.5-fold), it resulted in an increase of approximately 3-fold of the GAG to collagen type I ratio. Therefore, in the potential pharmacotherapy of OI type I with flavonoids, their effect on GAG level may be of importance. In the OI cells, some of the tested flavonoids applied at a concentration of 30 µM affected GAG content in quite the opposite way than type I collagen. Aglicones inhibiting collagen synthesis caused a marked increase in GAG concentration in medium, in contrast to the flavonoid glycosides, which exerted a stimulatory effect on type I collagen synthesis, but had a different effect on GAG content and distribution. Among these, apigenin 7-O-methylglucuronide did not affect GAG level or secretion, and thus may potentially be used in OI type I pharmacotherapy in patients with normal GAG content. However, in patients with increased concentrations of GAG, pectolinarin, which decreases GAG content by approximately 40%, may be more beneficial.