ECTS Abstracts (2015) 1 P240

Modulation of Osteoblast-Related Genes in Fibroblasts by Homocysteine and Bisphosphonates

Wolfgang Brozek1, Norbert Hassler1, Franz Varga1, Dimitris Tatakis2, Klaus Klaushofer1 & Eleftherios P Paschalis1

1Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of the WGKK and AUVA Trauma Center, 1st Medical Department at Hanusch Hospital, Vienna, Austria; 2Periodontology, College of Dentistry, The Ohio State University, Columbus, Ohio, USA.

The aim of the present study was to examine effects of homocysteine (Hcys), and bisphosphonates (BPs) on fibroblast gene expression for exploring its potential utility as surrogate for monitoring bone matrix quality. NIH-3T3 mouse fibroblast cells were cultured for six days in the presence/ absence of one of the most widely used bisphosphonates in osteoporosis management (alendronate, ibandronate, risedronate; 1 μM), with/without 4 mM Hcys. Following cell lysis and total RNA extraction, reverse transcriptase real-time PCR was performed on extracts of three independent experiments, data of which were evaluated using Student’s paired t-test. We identified a number of genes affecting bone quality and implicated in osteoporosis whose expression was statistically significantly modulated by Hcys and BPs in fibroblasts. Effects included down-regulation of Il6 by Hcys by one third (p<0.05) relative to untreated control cell cultures as well as up-regulation of lysyl oxidase (Lox) and periostin (Postn) in response to Hcys in combination with either alendronate or ibandronate by 1.5-fold to 2.2-fold (p<0.05). Moreover, when cells were incubated with Hcys plus risedronate, a similar effect was observed on Igf1 (insulin-like growth factor 1) expression, which was increased 2.4-fold (p<0.05) compared with untreated control. The results show that fibroblasts are responsive to stimuli that osteoblasts are exposed to in osteoporosis. Interestingly, in osteoblasts the opposite effects of Hcys alone on Il6 expression (up-regulation) and Lox expression (down-regulation) to the ones found herein were described previously. Moreover, elevated serum POSTN levels and decreased serum IGF-1 concentrations have been linked to increased fracture risk and osteoporosis, respectively. Since fibroblasts are responsive to both Hcys and bisphosphonates, skin organic matrix quality might be reflective of bone organic matrix quality both in disease and under treatment.

Disclosure: The authors declared no competing interests.

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