Superoxide dismutase 3 is expressed in bone tissue and required for normal bone homeostasis and mineralization

TY - JOUR

T1 - Superoxide dismutase 3 is expressed in bone tissue and required for normal bone homeostasis and mineralization

AU - Matthiesen, Cecilie L.

AU - Hu, Lili

AU - Torslev, Astrid S.

AU - Poulsen, Ebbe T.

AU - Larsen, Ulrike G.

AU - Kjaer-Sorensen, Kasper

AU - Thomsen, Jesper S.

AU - Brüel, Annemarie

AU - Enghild, Jan J.

AU - Oxvig, Claus

AU - Petersen, Steen V.

PY - 2021/2

Y1 - 2021/2

N2 - 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.

AB - 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.

KW - Bone homeostasis

KW - Bone mineralization

KW - Redox regulation

KW - Superoxide dismutase 3 (SOD3)

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=85099872800&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2021.01.027

DO - 10.1016/j.freeradbiomed.2021.01.027

M3 - Journal article

C2 - 33476796

AN - SCOPUS:85099872800

SN - 0891-5849

VL - 164

SP - 399

EP - 409

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -