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Carbonic anhydrase III protects osteocytes from oxidative stress
Author(s) -
Shi Chao,
Uda Yuhei,
Dedic Christopher,
Azab Ehab,
Sun Ningyuan,
Hussein Amira I.,
Petty Christopher A.,
Fulzele Keertik,
MitterbergerVogt Maria C.,
Zwerschke Werner,
Pereira Renata,
Wang Kunzheng,
Pajevic Paola Divieti
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700485rr
Subject(s) - oxidative stress , carbonic anhydrase , chemistry , oxidative phosphorylation , microbiology and biotechnology , biochemistry , biology , enzyme
Osteocytes are master orchestrators of bone remodeling; they control osteoblast and osteoclast activities both directly via cell‐to‐cell communication and indirectly via secreted factors, and they are the main postnatal source of sclerostin and RANKL (receptor activator of NF‐kB ligand), two regulators of osteoblast and osteoclast function. Despite progress in understanding osteocyte biology and function, much remains to be elucidated. Recently developed osteocytic cell lines—together with new genome editing tools—has allowed a closer look at the biology and molecular makeup of these cells. By using single‐cell cloning, we identified genes that are associated with high Sost/sclerostin expression and analyzed their regulation and function. Unbiased transcriptome analysis of high‐ vs. low‐Sost/ sclerostin‐expressing cells identified known and novel genes. Dmp1 (dentin matrix protein 1), Dkk1 (Dickkopf WNT signaling pathway inhibitor 1), and Phex were among the most up‐regulated known genes, whereas Srpx2, Cd200, and carbonic anhydrase III (CAIII) were identified as novel markers of differentiated osteocytes. Aspn, Enpp2, Robo2, Nov, and Serpina3g were among the transcripts that were most significantly suppressed in high‐Sost cells. Considering that CAII was recently identified as being regulated by Sost/sclerostin and capable of controlling mineral homeostasis, we focused our attention on CAIII. Here, we report that CAIII is highly expressed in osteocytes, is regulated by parathyroid hormone both in vitro and in vivo , and protects osteocytes from oxidative stress.—Shi, C., Uda, Y., Dedic, C., Azab, E., Sun,N.,Hussein,A.I.,Petty,C.A.,Fulzele,K.,Mitterberger‐Vogt,M.C.,Zwerschke,W.,Pereira,R.,Wang,K.,Divieti Pajevic, P. Carbonic anhydrase III protects osteocytes from oxidative stress. FASEB J. 32,440‐452 (2018). www.fasebj.org