1519 Nifedipine Induces Expression of Periostin and αSMA in Gingival Tissue

Saturday, March 24, 2012: 9:45 a.m. - 11 a.m.
Presentation Type: Poster Session
S. KIM, Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada, L. JACKSON-BOETERS, Department of Pathology, University of Western Ontario, London, ON, Canada, M. DARLING, Dept. of Pathology, Division of Oral Pathology, University of Western Ontario, London, ON, Canada, M. RIEDER, Department of Paediatrics, University of Western Ontario, London, ON, Canada, and D. HAMILTON, University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON, Canada
Objective: Gingival overgrowth, a fibrotic condition, is a serious side-effect commonly caused by the administration of nifedipine (NIF), which is a widely utilized drug for cardiac disorders. Nifedipine-induced gingival fibrosis (NIGF) is characterized as excess extracellular matrix (ECM) production and myofibroblast differentiation, but the pathogenesis is currently not understood. Periostin, a pro-fibrotic matricellular protein, has recently been recognized to promote collagen production and myofibroblast differentiation, leading to connective tissue compaction and fibrosis. In this study, we investigated whether periostin is associated with development of NIGF by examining periostin and other associated molecules such as α-Smooth Muscle Actin (αSMA), Focal Adhesion Kinase (FAK), and extracellular signal-regulated kinases 1/2 (ERK1/2).

Method: Gingival tissue samples were obtained from patients undergoing hypertension therapy with NIF (n=5), and control patients (n=4) who are systematically healthy. Tissues were examined, via immunohistochemistry, for periostin and αSMA proteins. Cultured healthy gingival fibroblasts were treated with NIF (30 ng/ml and 100 ng/ml) then RT-PCR and Western blotting were used to analyze changes in periostin expression. Changes in αSMA expression, as well as FAK and ERK1/2 activations were also examined using western blotting.

Result: All the diseased tissues demonstrated markedly increased periostin immunoreactivity compared to the healthy tissues, particularly in the ECM-rich, deep connective tissue. Furthermore, both periostin mRNA (p < 0.05) and protein expression increased in gingival fibroblasts cultured with NIF. NIF also increases αSMA expression and ERK1/2 activation of the cultured fibroblasts in vitro. However, ERK1/2 inhibition did not attenuate NIF-induced αSMA expression.

Conclusion: These results show that NIF directly induces periostin and αSMA expression in gingival fibroblasts. Considering periostin’s role in other fibrotic diseases and its over-expression in NIGF, this study may suggest a new therapeutic target for blocking development of gingival overgrowth.

This abstract is based on research that was funded entirely or partially by an outside source: Institute of Musculoskeletal Health and Arthritis Operating Grant (MH-94010) Canadian Foundation for Innovation Leaders Opportunities Fund (18742) Ontario Graduate Scholarship

Keywords: Extracellular matrix molecules, Fibroblasts, Fibrosis, Molecular biology and Periodontal disease