Preventive CCL2/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheumatoid Arthritis by Reducing Homing of CCR2 Osteoclast Progenitors to the Affected Bone.

Detailed characterization of medullary and extramedullary reservoirs of osteoclast progenitors (OCPs) is required to understand the pathophysiology of increased periarticular and systemic bone resorption in arthritis. In this study, we focused on identifying the OCP population specifically induced by arthritis and the role of circulatory OCPs in inflammatory bone loss. In addition, we determined the relevant chemokine axis responsible for their migration, and targeted the attraction signal to reduce bone resorption in murine collagen-induced arthritis (CIA).

Combined manual and automated immunophenotypisation identified disease-specific peripheral blood immune subpopulations in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.

Objectives: Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are associated with abnormal immune cell functions. We combined manual and automated profiling in subpopulations of T-cells, B-cells and monocytes, in parallel to functional testing and clinical correlation.

Methods: Using flow cytometry, we analysed the expression of CCR4, CCR6 and CXCR5 on helper and cyotoxic T-cells, CD32B and CD86 on naïve and memory B-cells, and CCR1, CCR2, CCR4 and CXCR4 on monocytes in chronic high-disease activity patients to identify peripheral blood subpopulations.

Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells.

Background: The peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA).

Methods: PB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy.

Advanced Clinical and Radiological Features of Ankylosing Spondylitis: Relation to Gender, Onset of First Symptoms and Disease Duration.

To determine the frequency of advanced clinical and radiological features of AS with reference to gender, onset of symptoms and disease duration. Fifty-seven patients diagnosed with AS were included in this study. Functional evaluation of the musculoskeletal system detected advanced clinical features: rubber-ball phenomenon, flattening of the chest anterior wall, diastasis of rectus abdominis muscle, steel back phenomenon, umbilical extrusion, skiing posture.

Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis.

The inflammatory milieu favors recruitment and activation of osteoclasts, and leads to bone destruction as a serious complication associated with arthritis and with other inflammatory processes. The frequency and activity of osteoclast progenitors (OCPs) correspond to arthritis severity, and may be used to monitor disease progression and bone resorption, indicating the need for detailed characterization of the discrete OCP subpopulations. Collectively, current studies suggest that the most potent murine bone marrow OCP population can be identified among lymphoid negative population within the immature myeloid lineage cells, as B220(-)CD3(-)CD11b(-/lo)CD115(+)CD117(+)CX3CR1(+) and possibly also Ter119(-)CD11c(-)CD135(lo)Ly6C(+)RANK(-).