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 regulating 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 earlier reported transgenic medaka lines expressing the osteoclast-inducing factor Receptor Activator of Nuclear Factor kB 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 osteoporosis patients. In an attempt to establish the medaka as 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 anti-resorptive or bone anabolic compounds by live imaging, and for screening of novel osteoporosis drugs.
Live imaging of osteoclast inhibition by bisphosphonates in a medaka osteoporosis model
present address: Department of Chemistry and Food Chemistry, TU Dresden, Dresden, Germany
present address: Faculty of Biology, VNU University of Science, Hanoi, Vietnam
Currently Viewing Accepted Manuscript - Newer Version Available
Tingsheng Yu, Paul Eckhard Witten, Ann Huysseune, Anita Buettner, Thuy Thanh To, Christoph Winkler; Live imaging of osteoclast inhibition by bisphosphonates in a medaka osteoporosis model. Dis Model Mech 2015; dmm.019091. doi: https://doi.org/10.1242/dmm.019091
Download citation file:
Advertisement
Valuing peer review at Disease Models & Mechanisms
We would like to thank our peer reviewers who contributed their time and expertise in 2023. In her latest Editorial, Editor-in-Chief Liz Patton has outlined why we continue to value our peer reviewers dedication.
Subject collection: Building advocacy into research
DMM’s new series - Building advocacy into research - features interviews, ‘The Patient’s Voice’, with patients and advocates for a range of disease types, with the aim of supporting the highest quality research for the benefit of all patients affected by disease.
Travelling Fellowships for early-career researchers
DMM and its sister journals offer Travelling Fellowships of up to £3,000 to graduate students and post-doctoral researchers wishing to make collaborative visits to other laboratories. Find out more about our Travelling Fellowships and read stories from previous grant recipients.
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.
The Forest of Biologists
Our Publisher Claire Moulton recently visited the two Woodland Trust UK sites where we are planting new native trees for published Research and Review papers and protecting ancient woodland on behalf of our peer reviewers.
Other journals from
The Company of Biologists