Gut-derived serotonin contributes to bone deficits in colitis

B. Lavoie, J. A. Roberts, M. M. Haag, S. N. Spohn, K. G. Margolis, K. A. Sharkey, J. B. Lian, G. M. Mawe

Research output: Contribution to journalArticlepeer-review

Abstract

Osteoporosis and bone fractures occur at higher frequency in patients with inflammatory bowel disease (IBD), and decreased bone mass is observed in animal models of colitis. Another consistent feature of colitis is increased serotonin (5-HT) availability in the intestinal mucosa. Since gut-derived 5-HT can decrease bone mass, via activation of 5-HT1B receptors on pre-osteoblasts, we tested the hypothesis that 5-HT contributes to bone loss in colitis. Colitis was chronically induced in mice by adding dextran sodium sulfate (DSS) to their drinking water for 21 days. At day 21, circulating 5-HT levels were elevated in DSS-inflamed mice. Micro-computed tomography of femurs showed a decrease in trabecular bone volume fraction, formation, and surface area, due largely to decreased trabecular numbers in DSS-treated mice. The colitis-induced loss of trabecular bone was significantly suppressed in mice treated with the 5-HT synthesis inhibitor, p-chloro-DL-phenylalanine (PCPA; 300 mg/kg/day IP daily), and in mice treated with the 5-HT1B receptor antagonist GR55562 (1 mg/Kg/day SC daily). The 5-HT reuptake transporter (SERT) is critical for moving 5-HT from the interstitial space into enterocytes and from serum into platelets. Mice lacking SERT exhibited significant deficits in trabecular bone mass that are similar to those observed in DSS-inflamed mice, and these deficits were not extensively worsened by DSS-induced colitis in the SERT−/− mice. Taken together, findings from both the DSS and SERT−/− mouse models support a contributing role for 5-HT as a significant factor in bone loss induced by colitis.

Original languageEnglish (US)
Pages (from-to)75-84
Number of pages10
JournalPharmacological Research
Volume140
DOIs
StatePublished - Feb 2019

Keywords

  • 5-HT receptor
  • bone loss
  • DSS-induced colitis
  • Peripheral 5-HT

ASJC Scopus subject areas

  • Pharmacology

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