High-throughput in vivo screening for bone anabolic compounds with zebrafish.
Osteoporosis and diseases of bone loss are a major public health problem for the present and the future since longevity and prevalence of the disease are increasing in all parts of the world. The bisphosphonates, widely used in the treatment of osteoporosis, act by inhibiting bone resorption. However, there are few agents that promote or increase bone formation in patients who have suffered substantial bone loss. To facilitate the identification of novel anabolic therapies, the authors have developed a rapid, high-throughput in vivo screen using larval zebrafish (Danio rerio) in which they are able to identify agents with anabolic effects in the skeleton within a 6-day time period. Vitamin D3 analogs and intermittent parathyroid hormone (PTH) result in dose-dependent increases in the formation of mineralized bone, whereas continuous exposure to PTH results in net bone loss. Because this model is fast, economical, and genetically tractable, it provides a powerful adjunct to mammalian models for the identification of new anabolic bone agents and offers the potential for genetic elucidation of pathways important in osteoblastic activity.
Fleming
Angeleen
A
DanioLabs Ltd., Cambridge, UK. angeleen.fleming@daniolabs.com
Sato
Masahiko
M
Goldsmith
Paul
P
D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000502:physiology; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D012968:Etidronic Acid / Q000494:pharmacology / Q000627:therapeutic use; D005240:Feasibility Studies; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D023421:Models, Animal; D010006:Osteoblasts / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use; D015027:Zebrafish
D050071:Bone Density Conservation Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010281:Parathyroid Hormone; D002762:Cholecalciferol; D012968:Etidronic Acid