PUBLICATION
Superoxide dismutase 3 is expressed in bone tissue and required for normal bone homeostasis and mineralization
- Authors
- Matthiesen, C.L., Hu, L., Torslev, A.S., Poulsen, E.T., Larsen, U.G., Kjaer-Sorensen, K., Thomsen, J.S., Brüel, A., Enghild, J.J., Oxvig, C., Petersen, S.V.
- ID
- ZDB-PUB-210123-14
- Date
- 2021
- Source
- Free radical biology & medicine 164: 399-409 (Journal)
- Registered Authors
- Keywords
- Superoxide dismutase 3 (SOD3), bone homeostasis, bone mineralization, redox regulation, zebrafish
- MeSH Terms
-
- Superoxide Dismutase*/genetics
- Superoxide Dismutase*/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Mice
- Animals
- Bone and Bones/metabolism
- Homeostasis
- Oxidation-Reduction
- PubMed
- 33476796 Full text @ Free Radic. Biol. Med.
Citation
Matthiesen, C.L., Hu, L., Torslev, A.S., Poulsen, E.T., Larsen, U.G., Kjaer-Sorensen, K., Thomsen, J.S., Brüel, A., Enghild, J.J., Oxvig, C., Petersen, S.V. (2021) Superoxide dismutase 3 is expressed in bone tissue and required for normal bone homeostasis and mineralization. Free radical biology & medicine. 164:399-409.
Abstract
Superoxide dismutase 3 (SOD3) is an extracellular protein with the capacity to convert superoxide into hydrogen peroxide, an important secondary messenger in redox regulation. To investigate the utility of zebrafish in functional studies of SOD3 and its relevance for redox regulation, we have characterized the zebrafish orthologues; Sod3a and Sod3b. Our analyses show that both recombinant Sod3a and Sod3b express SOD activity, however, only Sod3b is able to bind heparin. Furthermore, RT-PCR analyses reveal that sod3a and sod3b are expressed in zebrafish embryos and are present primarily in separate organs in adult zebrafish, suggesting distinct functions in vivo. Surprisingly, both RT-PCR and whole mount in situ hybridization showed specific expression of sod3b in skeletal tissue. To further investigate this observation, we compared femoral bone obtained from wild-type and SOD3-/- mice to determine whether a functional difference was apparent in healthy adult mice. Here we report, that bone from SOD3-/- mice is less mineralized and characterized by significant reduction of cortical and trabecular thickness in addition to reduced mechanical strength. These analyses show that SOD3 plays a hitherto unappreciated role in bone development and homeostasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping