RRC ID 47964
著者 Yu T, Witten PE, Huysseune A, Buettner A, To TT, Winkler C.
タイトル Live imaging of osteoclast inhibition by bisphosphonates in a medaka osteoporosis model.
ジャーナル Dis Model Mech
Abstract Osteoclasts are bone-resorbing cells derived from the monocyte/macrophage lineage. Excess osteoclast activity leads to reduced bone mineral density, a hallmark of diseases such as osteoporosis. Processes that regulate osteoclast activity are therefore targeted in current osteoporosis therapies. To identify and characterize drugs for treatment of bone diseases, suitable in vivo models are needed to complement cell-culture assays. We have previously reported transgenic medaka lines expressing the osteoclast-inducing factor receptor activator of nuclear factor κB ligand (Rankl) under control of a heat shock-inducible promoter. Forced Rankl expression resulted in ectopic osteoclast formation, as visualized by live imaging in fluorescent reporter lines. This led to increased bone resorption and a dramatic reduction of mineralized matrix similar to the situation in humans with osteoporosis. In an attempt to establish the medaka as an in vivo model for osteoporosis drug screening, we treated Rankl-expressing larvae with etidronate and alendronate, two bisphosphonates commonly used in human osteoporosis therapy. Using live imaging, we observed an efficient, dose-dependent inhibition of osteoclast activity, which resulted in the maintenance of bone integrity despite an excess of osteoclast formation. Strikingly, we also found that bone recovery was efficiently promoted after inhibition of osteoclast activity and that osteoblast distribution was altered, suggesting effects on osteoblast-osteoclast coupling. Our data show that transgenic medaka lines are suitable in vivo models for the characterization of antiresorptive or bone-anabolic compounds by live imaging and for screening of novel osteoporosis drugs.
巻・号 9(2)
ページ 155-63
公開日 2016-2-1
DOI 10.1242/dmm.019091
PII dmm.019091
PMID 26704995
PMC PMC4770141
MeSH Animals Diphosphonates / pharmacology* Disease Models, Animal* Oryzias Osteoclasts / drug effects* Osteoclasts / pathology Osteoporosis / pathology* RANK Ligand / metabolism*
IF 4.651
引用数 16
WOS 分野 PATHOLOGY CELL BIOLOGY
リソース情報
メダカ rankl:HSE:CFP (TG1135) ctsk:nlGFP (TG1132) rankl:HSE:CFP/ctsk:nlGFP (TG1139) osx:mCherry (TG1134)