Abstract:
:The primitive neurohypophyseal nonapeptide oxytocin (OXT) has established functions in parturition, lactation, appetite, and social behavior. We have shown that OXT has direct actions on the mammalian skeleton, stimulating bone formation by osteoblasts and modulating the genesis and function of bone-resorbing osteoclasts. We deleted OXT receptors (OXTRs) selectively in osteoblasts and osteoclasts using Col2.3Cre and Acp5Cre mice, respectively. Both male and female Col2.3Cre + :Oxtr fl/fl mice recapitulate the low-bone mass phenotype of Oxtr +/- mice, suggesting that OXT has a prominent osteoblastic action in vivo. Furthermore, abolishment of the anabolic effect of estrogen in Col2.3Cre + :Oxtr fl/fl mice suggests that osteoblastic OXTRs are necessary for estrogen action. In addition, the high bone mass in Acp5Cre + :Oxtr fl/fl mice indicates a prominent action of OXT in stimulating osteoclastogenesis. In contrast, we found that in pregnant and lactating Col2.3Cre + :Oxtr fl/fl mice, elevated OXT inhibits bone resorption and rescues the bone loss otherwise noted during pregnancy and lactation. However, OXT does not contribute to ovariectomy-induced bone loss. Finally, we show that OXT acts directly on OXTRs on adipocytes to suppress the white-to-beige transition gene program. Despite this direct antibeiging action, injected OXT reduces total body fat, likely through an action on OXT-ergic neurons. Consistent with an antiobesity action of OXT, Oxt -/- and Oxtr -/- mice display increased total body fat. Overall, the actions of OXT on bone mass and body composition provide the framework for future therapies for osteoporosis and obesity.
journal_name
Proc Natl Acad Sci U S Aauthors
Sun L,Lizneva D,Ji Y,Colaianni G,Hadelia E,Gumerova A,Ievleva K,Kuo TC,Korkmaz F,Ryu V,Rahimova A,Gera S,Taneja C,Khan A,Ahmad N,Tamma R,Bian Z,Zallone A,Kim SM,New MI,Iqbal J,Yuen T,Zaidi Mdoi
10.1073/pnas.1913611116subject
Has Abstractpub_date
2019-12-16 00:00:00eissn
0027-8424issn
1091-6490pii
1913611116pub_type
杂志文章abstract::(3)H-actinomycin D, a guanine-binding agent, labels fixed human chromosomes nonrandomly. Actinomycin D added in G2 inhibits secondary constrictions and breaks chromosomes. There is some tendency for label to be concentrated at the ends of chromosomes and near the centromere. Labeling with (3)H-thymidine in the late st...
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