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Increased Serotonin Availability Contributes to Decreased Bone Density in Colitis
Author(s) -
Lavoie Brigitte,
Roberts Jane,
Spohn Stephanie,
Sharkey Keith,
Lian Jane,
Mawe Gary
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.854.5
Subject(s) - serotonin , endocrinology , medicine , colitis , chemistry , bone density , antagonist , stimulation , receptor , osteoporosis
The link between inflammatory bowel disease (IBD) and decreased bone density is not completely understood. It is known that serotonin can have a negative impact on bone formation via preosteoblast 5‐HT 1B stimulation, and that serotonin‐selective reuptake transporter (SERT) expression is decreased in inflamed intestinal epithelium, leading to increases in 5‐HT entering the blood stream from the gut. Therefore, we tested the hypothesis that 5‐HT acting on 5‐HT 1B receptors is a contributing factor in colitis‐related bone formation deficits. Colitis was induced by adding dextran sodium sulfate (DSS) to the drinking water of BALB/c mice for 21 days (5% for 7 days and then 1%). Some animals also received the 5‐HT 1B antagonist, GR55562 (1 mg/kg/day SC). DSS mice serum had higher 5‐HT levels compared to control. Femurs were analyzed by micro‐computed tomography. DSS treated mice exhibited a marked decrease in bone density, including significant deceases in bone volume fraction, density, trabecular number and bone surface, and increased trabecular spacing. Treatment with the 5‐HT 1B antagonist improved all of these features of bone formation. Dynamic bone growth was evaluated by dual injections of calcein 4 days apart and the spacing of fluorescent bands was found to be significantly reduced in DSS mice, but comparable to control values in DSS mice treated with the 5‐HT 1B antagonist. In conclusion, these findings support the novel concept that altered 5‐HT handling in the gut can be a contributing factory in colitis‐induced changes bone density. Supported by DK62267