RRC ID 30223
Author To TT, Witten PE, Renn J, Bhattacharya D, Huysseune A, Winkler C.
Title Rankl-induced osteoclastogenesis leads to loss of mineralization in a medaka osteoporosis model.
Journal Development
Abstract Osteoclasts are macrophage-related bone resorbing cells of hematopoietic origin. Factors that regulate osteoclastogenesis are of great interest for investigating the pathology and treatment of bone diseases such as osteoporosis. In mammals, receptor activator of NF-κB ligand (Rankl) is a regulator of osteoclast formation and activation: its misexpression causes osteoclast stimulation and osteoporotic bone loss. Here, we report an osteoporotic phenotype that is induced by overexpression of Rankl in the medaka model. We generated transgenic medaka lines that express GFP under control of the cathepsin K promoter in osteoclasts starting at 12 days post-fertilization (dpf), or Rankl together with CFP under control of a bi-directional heat-shock promoter. Using long-term confocal time-lapse imaging of double and triple transgenic larvae, we monitored in vivo formation and activation of osteoclasts, as well as their interaction with osteoblasts. Upon Rankl induction, GFP-positive osteoclasts are first observed in the intervertebral regions and then quickly migrate to the surface of mineralized neural and haemal arches, as well as to the centra of the vertebral bodies. These osteoclasts are TRAP (tartrate-resistant acid phosphatase) and cathepsin K positive, mononuclear and highly mobile with dynamically extending protrusions. They are exclusively found in tight contact with mineralized matrix. Rankl-induced osteoclast formation resulted in severe degradation of the mineralized matrix in vertebral bodies and arches. In conclusion, our in vivo imaging approach confirms a conserved role of Rankl in osteoclastogenesis in teleost fish and provides new insight into the cellular interactions during bone resorption in an animal model that is useful for genetic and chemical screening.
Volume 139(1)
Pages 141-50
Published 2012-1
DOI 10.1242/dev.071035
PII dev.071035
PMID 22096076
MeSH Acid Phosphatase / metabolism Animals Animals, Genetically Modified Bone Resorption / physiopathology* Cathepsin K / genetics Green Fluorescent Proteins / metabolism Isoenzymes / metabolism Microscopy, Confocal Oryzias Osteoclasts / cytology Osteoclasts / metabolism* Osteoporosis / physiopathology* Promoter Regions, Genetic / genetics RANK Ligand / metabolism* Tartrate-Resistant Acid Phosphatase Time-Lapse Imaging
IF 5.763
Times Cited 59
Medaka Hatching enzyme OK-Cab (MT830) rankl:HSE:CFP (TG1135) ctsk:mEGFP (TG1131)