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Cytochrome P450 Expression Revealed in Long Bone Growth Plates
Author(s) -
Panda Satya,
Kellogg Dean,
Tang Kejian,
Masters Bettie Sue
Publication year - 2015
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/fasebj.29.1_supplement.884.63
Subject(s) - endocrinology , cytochrome p450 , medicine , cyp1b1 , bone remodeling , bone cell , osteocyte , downregulation and upregulation , chemistry , retinoic acid , biology , osteoblast , biochemistry , metabolism , gene , in vitro
Cytochrome P450 oxidoreductase (POR) donates electrons to endoplasmic reticulum‐resident cytochromes P450 (CYPs), heme oxygenase (HO), and dehydrocholesterol reductase for catalytic function. CYPs are necessary for the metabolism of cholesterol, steroids, sex hormones, as well as drugs and toxins. Thus, alterations in POR activity have multiple effects on the physiological activities of these metabolites. Human mutations in POR have been reported and present as altered steroidogenic profiles, severe craniofacial and bone defects resembling Antley‐Bixler syndrome (ABS). A publication from our group using a bone‐specific, POR‐deleted mouse model has shown that POR deletion from bone leads to defects in both skull development and long bone trabecular bone density, as measured by micro computed tomography (µCT) analysis. These bone defects are most likely due to altered fibroblast growth factor‐mediated signaling including upregulation of Runx2, Sp7 and downregulation of Sprouty, in long bone. This suggests a role for the POR/CYP system in the bone during development and growth. Many circulating CYP metabolites are known to be critical in bone development, namely retinoic acid, cholesterol, vitamin D, estrogen, etc. However, the presence of CYPs in bone, as well as their roles, is not well characterized except for the presence of CYP19. Our data reveal CYPs 1A2, 17A1, 19, 2E1, 26A1 and weaker 2R1 expression in the growth plate of mouse long bone. The initial findings show a decreased expression of CYP1A2, as well as CYP19, in our bone‐specific POR knockdown; however, no decrease in CYP2R1 expression was noticed. Expression of CYPs in primary osteoblasts, osteoblast cell lines and their potential functions in bone development are being examined. NIH GM081568 to BSSM and SPP.