Neutrophil extracellular traps mediate bone erosion in rheumatoid arthritis by enhancing RANKL-induced osteoclastogenesis.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause bone erosion due to increased osteoclastogenesis. Neutrophils involvement in osteoclastogenesis remains uncertain. Given that neutrophil extracellular traps (NETs) can act as inflammatory mediators in rheumatoid arthritis, we investigated the role of NETs in stimulating bone loss by potentiating osteoclastogenesis during arthritis. EXPERIMENTAL APPROACH: The level of NETs in synovial fluid from arthritis patients was assessed. Bone loss was evaluated by histology and micro-CT in antigen-induced arthritis (AIA)-induced WT mice treated with DNase or in Padi4-deficient mice (Padi4flox/flox LysMCRE ). The size and function of osteoclasts and the levels of RANKL and osteoprotegerin (OPG) released by osteoblasts that were incubated with NETs were measured. The expression of osteoclastogenic marker genes and protein levels were evaluated by qPCR and western blotting. To assess the participation of TLR4 and TLR9 in osteoclastogenesis, cells from Tlr4-/- and Tlr9-/- mice were cultured with NETs. KEY RESULTS: Rheumatoid arthritis patients had higher levels of NETs in synovial fluid than osteoarthritis patients, which correlated with increased levels of RANKL/OPG. Moreover, patients with bone erosion had higher levels of NETs. Inhibiting NETs with DNase or Padi4 deletion alleviated bone loss in arthritic mice. Consistently, NETs enhanced RANKL-induced osteoclastogenesis that was dependent on TLR4 and TLR9 and increased osteoclast resorptive functions in vitro. In addition, NETs stimulated the release of RANKL and inhibited osteoprotegerin in osteoblasts, favouring osteoclastogenesis. CONCLUSIONS AND IMPLICATIONS: Inhibiting NETs could be an alternative strategy to reduce bone erosion in arthritis patients.

Multiple Factors Involved in Bone Damage Caused by Chikungunya Virus Infection.

Chronic cases of chikungunya fever represent a public health problem in countries where the virus circulates. The disease is prolonged, in some cases, for years, resulting in disabling pain and bone erosion among other bone and joint problems. As time progresses, tissue damage is persistent, although the virus has not been found in blood or joints. The pathogenesis of these conditions has not been fully explained. Additionally, it has been considered that there are multiple factors that might intervene in the viral pathogenesis of the different conditions that develop. Other mechanisms involved in osteoarthritic diseases of non-viral origin could help explain how damage is produced in chronic conditions. The aim of this review is to analyze the molecular and cellular factors that could be involved in the tissue damage generated by different infectious conditions of the chikungunya virus.

Osteoinmunología: Una visión integrada de los sistemas inmunológico y óseo. Nuevas perspectivas de las enfermedades óseas / Osteoimmunology: An Integrated Vision of Immune and Bone Systems. Novel Perspectives for Bone Disease

Esta 3ª parte se propone comentar los mecanismos inmunológicos involucrados en el deterioro de la masa ósea en algunas enfermedades autoinmunes. Dado que estas son numerosas (múltiples componentes del Síndrome Poliglandular Autoinmune, Enfermedad celíaca, Síndrome de Crohn, colitis ulcerosa, HIV, patologías reumatológicas, anemia perniciosa, asma bronquial e incluso periodontitis), se eligieron cuatro afecciones que actualmente podrían tener un mayor interés: La Artritis Reumatoidea por ser la patología paradigmática del deterioro óseo; la posmenopausia, donde se describe poco el rol autoinmune; el HIV, por la prolongada sobrevida actual con mayores posibilidades de lesiones óseas y la Periodontitis, como una incursión en el compromiso odontológico, a veces poco conocido por el médico. En muchos casos el conocimiento de estos mecanismos ha contribuido a la generación de medicamentos específicos logrando éxitos terapéuticos con mejor calidad de vida. Rev Argent Endocrinol Metab 51:197-204, 2014 Los autores declaran no poseer conflictos de interés.

The objective of this communication is to review the immune mechanisms involved in the pathogenesis of bone damage in some autoimmune diseases. As they are numerous (autoimmune polyendocrinopathy , celiac disease, Crohn's disease, ulcerative colitis, HIV, rheumatic diseases, bronchial asthma, pernicious anemia, periodontitis, etc.), we selected only four: Rheumatoid Arthritis, because of its typical bone lesions; post­menopause, because the immune components are not so often described; HIV, because of the current longer survival time with higher possibilities of bone lesions, and Periodontitis, in order to have an overview of dental aspects of this pathology. In many cases, knowledge of these mechanisms has contributed to the de­velopment of specific drugs that have led to therapeutic success and an improved quality of life. Rev Argent Endocrinol Metab 51:197-204, 2014 No finantial conflicts of interest exist.