Role of osteoclastogenesis and osteoclasts activation in patients with ankylosing spondylitis

• Grant number: 11/23781-2
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2012
• End date: January 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rosa Maria Rodrigues Pereira
• Grantee: Rosa Maria Rodrigues Pereira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by new bone formation leading to subsequent development of syndesmophytes and spinal ankylosis. Concomitantly, patients with AS have low bone mass and patients with syndesmophytes have lower bone density compared with patients without this complication. These findings reinforce the idea that the formation and bone loss can occur in parallel in the EA and be related to the RANKL system imbalance, RANKL and osteoprotegerin (OPG).In the EA there is a strong association between the catabolic pathways (RANKL) and anabolic (Wnt). The latter is essential for the proliferation and differentiation of osteoblasts. Cytokines such as TNF induce DKK-1 and sclerostin, proteins that act by inhibiting the Wnt signaling pathway. The blockade of DKK-1 and / or sclerostin can lead to reduction in the number of osteoclasts and interfering in bone resorption and suggesting that the anabolic and catabolic pathways interact with important biological role. Molecularly, the OPG is a key component of RANK-RANKL system and appears to be regulated by the Wnt pathway and vice versa. Based on the knowledge that osteoclasts play a central role in osteo-articular destruction in inflammatory diseases, we question whether variations in osteoclastogenesis in patients with AS might be correlated to the presence, activity or disease severity. To this end, we propose the study of peripheral blood mononuclear cells of patients with EA to analyze the characteristics of osteoclast precursors, mature osteoclasts, and their ability osteoclastogenic correlate with clinical disease and bone mineral density in these patients. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CAPARBO, V. F.; SAAD, C. G. S.; MORAES, J. C.; DE BRUM-FERNANDES, A. J.; PEREIRA, R. M. R.. Monocytes from male patients with ankylosing spondylitis display decreased osteoclastogenesis and decreased RANKL/OPG ratio. OSTEOPOROSIS INTERNATIONAL, v. 29, n. 11, p. 2565-2573, NOV 2018. (11/23781-2)

CAPARBO, VALERIA F.; FURLAM, PEDRO; SAAD, CARLA G. S.; ALVARENGA, JACKELINE C.; AUBRY-ROZIER, BERENGERE; HANS, DIDIER; DE BRUM-FERNANDES, ARTUR J.; PEREIRA, ROSA M. R.. Assessing bone impairment in ankylosing spondylitis (AS) using the trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT). BONE, v. 122, p. 8-13, MAY 2019. (11/23781-2)