Poster Presentation 29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019

Potential regulatory role for serotonin in human osteoclastogenesis (#181)

Jasmine R Cleminson 1 2 , Jason M Hodge 2 3 4 , Julie A Pasco 1 2 5 , Fiona Collier 2 3 4 , Rasika Samarasinghe 3 , Lana J Williams 1 2 , Jasmine R Cleminson 1 2
  1. IMPACT SRC, School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria, Australia
  2. University Hospital Geelong, Barwon Health, Geelong, Victoria, Australia
  3. School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria, Australia
  4. Geelong Centre for Emerging Infectious Diseases, School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria, Australia
  5. Melbourne Medical School-Western Precinct, The University of Melbourne, St Albans, Victoria, Australia

Objectives: Mood disorders and selective serotonin reuptake inhibitors are implicated in bone loss and fracture risk. Serotonin acts centrally to regulate mood, and peripherally to control gut and cardiovascular function. A role for peripheral serotonin in bone homeostasis has been proposed. Transcription of genes for serotonin receptors and tryptophan hydroxylase (TPH1), a rate-limiting enzyme in serotonin biosynthesis, have been reported in both osteoblasts and osteoclasts (OC). This study investigated the transcription profile of serotonin receptor-2B (5-HTR2B) and TPH1 in human osteoclastogenesis and the impact of blocking serotonin biosynthesis using a chemical inhibitor of TPH1.

Methods: Human osteoclasts were generated from umbilical cord blood. CFU-GM–derived OC precursors were cultured in serotonin-depleted media containing RANKL and M-CSF for up to 21d. Gene transcription of 5-HTR2B and TPH1 was assessed by real-time PCR. In addition, OC precursors were cultured on dentine slices in the presence of TPH1 inhibitor (LP533401-HCl). Data were analysed using one-way ANOVA and Tukey’s Pairwise Comparisons.

Results: Multinucleated OCs were observed from day-6 of culture. Transcription of both 5-HTR2B and TPH1 peaked at day-14 (>7404-fold and >3.6-fold, respectively) and dropped to baseline levels by day-18. Co-treatment with LP533401-HCl dose-dependently decreased OC number and resorption, with maximum reductions of 59.7% (p=0.0001) and 40.9% (p=0.003), respectively, at 10mm, whereas OC size dramatically increased (+135.4%; p=0.0001).

Conclusion: These data indicate that human OCs may express serotonin receptor 2B and possess the ability to synthesise serotonin. The observed increase in OC fusion and reduction in resorption following chemical blockade of TPH1 point to a possible autocrine regulatory role for serotonin within the bone microenvironment.