title: Bisphosphonates modulate the expression of OPG and M-CSF in hMSC-derived osteoblasts.
abstract: Bisphosphonates have been known to suppress osteoclast activity, survival, and recruitment. In this study, we tested effects of BPs on expression of two critical genes for osteoclastogenesis, M-CSF, and OPG in the process of osteoblast differentiation from hMSC. (1) The cells were cultured in osteogenic induction medium together with 0 (control group) and 10-8 M alendronate, pamidronate for up 2 and 3 weeks (for real-time PCR) and 3 and 4 weeks (for ELISA). (2) The real-time PCR protocol for M-CSF, OPG, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) consist of 40 cycles. (3) Enzyme-linked immunosorbent assay (ELISA): the amounts of M-CSF and OPG in the culture medium were determined using commercially available ELISA kits for M-CSF and OPG. Treatment of differentiating cells with alendronate or pamidronate, nitrogen-containing BPs increase the expression of OPG, which suppresses osteoclastogenesis, whereas it decreases the expression of M-CSF, which enhances preosteoclast formation. These results suggest a new mechanism by which BPs inhibit osteoclastogenesis. Results support hypothesis that progressive accumulation of bisphosphonate in jaws causes imbalance in osteogenesis and bone absorption and collateral osteoclast-osteoblast interaction. Bisphosphonate-related osteonecrosis of jaw (BPONJ) is one of the most serious complications of bisphosphonate (BP) therapy. However, the mechanism behind the this process of BPONJ is still unclear and there are so many hypotheses. Among many hypotheses, we focused on osteoclast-osteoblast interaction in this study. The findings of this study show new light on the present BPONJ occurrence theory based on the osteoclastic activity of BPs. Also, a more advanced and developed theory for BRONJ occurrence may be obtained by combining the osteoclast inhibition mechanism and the effects on osteoblastic differentiation by BPs.
authors.affiliation: Department of Oral & Maxillofacial Surgery, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Ohe
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kwon
authors.forename: Hyeon-Woo
authors.initials: HW
authors.lastname: Lee
mesh_terms: D019386:Alendronate / Q000494:pharmacology; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000473:pathology; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D003470:Culture Media; D004164:Diphosphonates / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000187:drug effects; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000187:drug effects*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects; D010012:Osteogenesis / Q000502:physiology; D053244:Osteoprotegerin / Q000187:drug effects*; D000077268:Pamidronate; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D003470:Culture Media; D004164:Diphosphonates; D053244:Osteoprotegerin; D016173:Macrophage Colony-Stimulating Factor; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+); D000077268:Pamidronate; D019386:Alendronate