title: Decreased Serotonin Levels and Serotonin-Mediated Osteoblastic Inhibitory Signaling in Patients With Ankylosing Spondylitis.
abstract: Evidence suggests that serotonin is an inhibitor of bone formation. We aimed to assess: 1) serum serotonin levels in patients with ankylosing spondylitis (AS), a prototype bone-forming disease, compared with patients with rheumatoid arthritis (RA) and healthy subjects; 2) the effect(s) of TNFα blockers on serum serotonin levels in patients with AS and RA; and 3) the effect(s) of serum of AS patients on serotonin signaling. Serum serotonin levels were measured in 47 patients with AS, 28 patients with RA, and 40 healthy subjects by radioimmunoassay; t test was used to assess differences between groups. The effect of serum on serotonin signaling was assessed using the human osteoblastic cell line Saos2, evaluating levels of phospho-CREB by Western immunoblots. Serotonin serum levels were significantly lower in patients with AS compared with healthy subjects (mean ± SEM ng/mL 122.9 ± 11.6 versus 177.4 ± 24.58, p = 0.038) and patients with RA (mean ± SEM ng/mL 244.8 ± 37.5, p = 0.0004). Patients with AS receiving TNFα blockers had significantly lower serotonin levels compared with patients with AS not on such treatment (mean ± SEM ng/mL 95.8 ± 14.9 versus 149.2 ± 16.0, p = 0.019). Serotonin serum levels were inversely correlated with pCREB induction in osteoblast-like Saos-2 cells. Serotonin levels are low in patients with AS and decrease even further during anti-TNFα treatment. Differences in serotonin levels are shown to have a functional impact on osteoblast-like Saos-2 cells. Therefore, serotonin may be involved in new bone formation in AS.
authors.affiliation: Division of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Klavdianou
authors.affiliation: Division of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece.
authors.forename: Stamatis-Nick
authors.initials: SN
authors.lastname: Liossis
authors.affiliation: Department of Anatomy-Histology-Embryology, Laboratory of Bone and Soft Tissue Studies, University of Patras Medical School, Patras, Greece.
authors.forename: Dionysios J
authors.initials: DJ
authors.lastname: Papachristou
authors.affiliation: Department of Gastroenterology, University of Patras Medical School, Patras University Hospital, Patras, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Theocharis
authors.affiliation: Clinical and Molecular Oncology Laboratory, University of Patras Medical School, Patras University Hospital, Patras, Greece.
authors.forename: Chaido
authors.initials: C
authors.lastname: Sirinian
authors.affiliation: Clinical and Molecular Oncology Laboratory, University of Patras Medical School, Patras University Hospital, Patras, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kottorou
authors.affiliation: Division of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Filippopoulou
authors.affiliation: Division of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Andonopoulos
authors.affiliation: Division of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Daoussis
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003424:Crohn Disease / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003710:Demography; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D012701:Serotonin / Q000097:blood*; D015398:Signal Transduction; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D017362:Cyclic AMP Response Element-Binding Protein; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase
keywords: ANKYLOSING SPONDYLITIS; ANTI-TNFα TREATMENT; NEW BONE FORMATION; OSTEOBLASTOGENESIS; SEROTONIN; SPONDYLOARTHROPATHIES; TNFα BLOCKER