The influence of bisphosphonates on human osteoblast migration and integrin aVb3/tenascin C gene expression in vitro

• Published in: Head & face medicine Vol. 7; no. 1; p. 4
• Main Authors: Koch, Felix P, Wunsch, Annette, Merkel, Christina, Ziebart, Thomas, Pabst, Andreas, Yekta, Sareh Said, Blessmann, Marco, Smeets, Ralf
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.02.2011; BioMed Central; BMC
• Subjects: Apoptosis; Cell adhesion; Cell adhesion & migration; Cell migration; Cell Movement - drug effects; Cell Movement - genetics; Chemical properties; Design; Diphosphonates; Diphosphonates - pharmacology; Dosage and administration; Experiments; Gene expression; Gene Expression - drug effects; Genetic aspects; Humans; Imidazoles - pharmacology; In Vitro Techniques; Influence; Integrin alphaVbeta3 - genetics; Integrins; Maxillofacial surgery; Osteoblasts - drug effects; Physiological aspects; Proteins; Standard deviation; Statistical analysis; Studies; Surgery; Tenascin - genetics; Germany
• ISSN: 1746-160X; 1746-160X
• DOI: 10.1186/1746-160X-7-4

Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods. By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10(-5)M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5 data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control. After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels. Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.