Decreased Serotonin Levels and Serotonin‐Mediated Osteoblastic Inhibitory Signaling in Patients With Ankylosing Spondylitis

• Published in: Journal of bone and mineral research Vol. 31; no. 3; pp. 630 - 639
• Main Authors: Klavdianou, Kalliopi, Liossis, Stamatis‐Nick, Papachristou, Dionysios J, Theocharis, Georgios, Sirinian, Chaido, Kottorou, Anastasia, Filippopoulou, Alexandra, Andonopoulos, Andrew P, Daoussis, Dimitrios
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.03.2016
• Subjects: Adult; ANKYLOSING SPONDYLITIS; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; ANTI‐TNFα TREATMENT; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Biomarkers - metabolism; Case-Control Studies; Cell Line; Cell Proliferation - drug effects; Crohn Disease - pathology; Cyclic AMP Response Element-Binding Protein - metabolism; Demography; Duodenum - drug effects; Duodenum - metabolism; Duodenum - pathology; Female; Humans; Inflammation - blood; Inflammation - complications; Male; Middle Aged; NEW BONE FORMATION; OSTEOBLASTOGENESIS; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteoblasts - pathology; Phosphorylation - drug effects; SEROTONIN; Serotonin - blood; Signal Transduction; Spondylitis, Ankylosing - blood; Spondylitis, Ankylosing - complications; Spondylitis, Ankylosing - drug therapy; Spondylitis, Ankylosing - metabolism; SPONDYLOARTHROPATHIES; TNFα BLOCKER; Tryptophan Hydroxylase - metabolism; Tumor Necrosis Factor-alpha; ANTI-TNFα TREATMENT; OSTEOBLASTOGENESIS; NEW BONE FORMATION; SEROTONIN; TNFα BLOCKER; ANKYLOSING SPONDYLITIS; SPONDYLOARTHROPATHIES
• ISSN: 0884-0431; 1523-4681; 1523-4681
• DOI: 10.1002/jbmr.2724

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. © 2015 American Society for Bone and Mineral Research.