Expression profile and synthesis of different collagen types I, II, III, and V of human gingival fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate treatment.
Bisphosphonates (BP) are used in the treatment of malignant osteolytic processes and postmenopausal osteoporosis. There have been a number of incidents in patients treated with BP. The incidents are described as an osteonecrosis of the jaw (ONJ). The main medications associated with these reports are zoledronic acid (ZOL) and pamidronate (PAM). The clinical presentations describe a deterioration of the jaw bones and surrounding tissues. The purpose of this study was to investigate expression of collagen types I, II, III, and V in human gingival fibroblasts, osteoblasts, and osteosarcoma cells (SaOS-2 cells) by ELISA and reverse transcription PCR (RT-PCR) with constant exposure (28 days) to ZOL and PAM. The real-time PCR indicates that ZOL inhibited gene expression below 16% at any concentration used. Hence, an amplification of extracellular matrix was only possible for PAM at concentrations of 1 microM. The following expression levels were for fibroblasts at a maximum of 31%, exceptionally high for the osteoblasts at 56%, and for SaOS-2 cells the peak was 14%. Principally, a decreased production of collagen was measured. With this in vitro study, we demonstrated how negatively influencing a long exposure to ZOL and PAM can be. Therefore, a reduction in extracellular matrix production of these cell lines under BP exposure could be a possible clinical indication as to why patients experience ONJ and have wound healing problems. However, it remains uncertain as to why an osteonecrosis is mainly found in the jaws and not other bones. As there are many influencing factors, further investigation needs to be pursued.
Simon
Maciej J K
MJ
Department of Oral and Maxillofacial Surgery, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, Kiel, Germany. maciej.simon@gmail.com
Niehoff
Peter
P
Kimmig
Bernhard
B
Wiltfang
Jörg
J
Açil
Yahya
Y
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004164:Diphosphonates / Q000009:adverse effects*; D024022:Fibrillar Collagens / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000096:biosynthesis; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D024022:Fibrillar Collagens; D015675:Osteocalcin; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D000469:Alkaline Phosphatase