An adult osteopetrosis model in medaka reveals the importance of osteoclast function for bone remodeling in teleost fish.
Osteoclasts play important roles during bone growth and in maintaining bone health and bone homeostasis. Dysfunction or lack of osteoclasts leads to increased bone mass and osteopetrosis phenotypes in mouse and human. Here we report a severe osteopetrosis-like phenotype in transgenic medaka fish, in which membrane bound EGFP (mEGFP) was expressed in osteoclasts under control of the cathepsin K promoter (ctsk:mEGFP). In contrast to reporter lines with GFP expression in the cytoplasm of osteoclasts, adult fish of the mEGFP line developed bone defects indicative for an osteoclast dysfunction. Activity of tartrate-resistant acid phosphatase (TRAP) was down-regulated and excess bone was observed in most parts of the skeleton. The osteopetrotic phenotype was particularly obvious at the neural and haemal arches that failed to increase their volume in growing fish. Excess bone caused severe constriction of the spinal cord and the ventral aorta. The continuation of tooth development and the failure to shed teeth resulted in severe hyperdontia. Interestingly, at the vertebral column vertebral body arches displayed a severe osteopetrosis, while vertebral centra had no or only a mild osteopetrotic phenotype. This confirms previous reports from cichlids that, different from the arches, allometric growth of fish vertebral centra initially does not depend on the action of osteoclasts. Independent developmental mechanism that shapes arches and vertebral centra can also lend support to the hypothesis that vertebral centra and arches function as independent developmental modules. Together, this medaka osteopetrosis model confirms the importance of proper osteoclast function during normal skeletal development in teleost fish that requires bone modeling and remodeling.
Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; NUS Centre for Bioimaging Sciences (CBIS), Singapore.
Thuy Thanh
TT
To
Department of Biology, University of Ghent, Belgium.
Paul Eckhard
PE
Witten
Department of Biology, University of Ghent, Belgium.
Ann
A
Huysseune
Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; NUS Centre for Bioimaging Sciences (CBIS), Singapore. Electronic address: dbswcw@nus.edu.sg.
Christoph
C
Winkler
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified / Q000502:physiology; D016723:Bone Remodeling / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009990:Oryzias / Q000378:metabolism / Q000502:physiology*; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D010022:Osteopetrosis / Q000378:metabolism / Q000503:physiopathology*; D010641:Phenotype; D000071681:Tartrate-Resistant Acid Phosphatase
D007527:Isoenzymes; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
Cathepsin K; Osteoblasts; Osteoclasts; Osteopetrosis; Osteoporosis; Vertebra; Vertebral arch; Vertebral centra