Periarticular Bone Loss in Antigen‐Induced Arthritis

Abstract

ObjectiveBone loss in arthritis is a complex process characterized by bone erosions and periarticular and generalized bone loss. The antigen-induced arthritis (AIA) model is mainly used to study synovitis and joint destruction, including bone erosions; however, periarticular bone loss has been less extensively investigated. The objectives of this study were to characterize and establish AIA as a model for periarticular bone loss, and to determine the importance of NADPH oxidase 2 (NOX-2)–derived reactive oxygen species (ROS) in periarticular bone loss.MethodsArthritis was induced in mice by local injection of antigen in one knee; the other knee was used as a nonarthritis control. At study termination, the knees were collected for histologic assessment. Periarticular bone mineral density (BMD) was investigated by peripheral quantitative computed tomography. Flow cytometric analyses were performed using synovial and bone marrow cells.ResultsAIA resulted in decreased periarticular trabecular BMD and increased frequencies of preosteoclasts, neutrophils, and monocytes in the arthritic synovial tissue. Arthritis induction resulted in an increased capability to produce ROS. However, induction of arthritis in Ncf1*/* mice, which lack NOX-2–derived ROS, and control mice resulted in similar reductions in periarticular trabecular BMD.ConclusionThe initiation of AIA resulted in periarticular bone loss associated with local effects on inflammatory cells and osteoclasts. Furthermore, based on our observations using this model, we conclude that NOX-2–derived ROS production is not essential for inflammation-mediated periarticular bone loss. Thus, AIA can be used as a model to investigate the pathogenesis of local inflammation–mediated bone loss.

Suppression of Experimental Arthritis and Associated Bone Loss by a Tissue-Selective Estrogen Complex

“…In accordance with preserved BMD, BZA/E2 reduced bone marrow preosteoclasts, defined as M-CSFR ϩ cells of the monocyte/macrophage population by using flow cytometry. Changes in levels of these bone marrow preosteoclasts have previously been reported to correspond with numbers of differentiated osteoclasts in situ in bone sections, as well as correspond with alterations in trabecular BMD, in mice with experimental arthritis (17,18). However, bone metabolism serum markers were not altered by any treatment in CIA, possibly due to the timing of serum sampling.…”

Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against Citrullinated Vimentin

“…AIA affects periarticular bone, as described . Therefore we investigated the cellular composition of immune cells in the periarticular bone marrow next to the injected knee joint as well as the draining inguinal lymph nodes.…”

“…Knee joints were fixed in 4% formalin, decalcified in EDTA (Sigma‐Aldrich), embedded in paraffin, and sectioned (2 µm). Sections were stained with hematoxylin and eosin, and synovitis, bone erosion, and cartilage destruction was graded as described . To determine the number of osteoclasts, sections were stained for tartrate resistant acid phosphatase (TRAP) using a Leukocyte Acid Phosphatase Kit (Sigma) as described .…”

“…To test this concept we used an experimental model of arthritis, which specifically leads to periarticular bone loss. Antigen‐induced arthritis (AIA) is characterized by local leukocyte infiltration and synovitis associated with periarticular bone loss . No systemic osteoporosis is observed in AIA.…”

Signalling in Neutrophils: A Retro Look

“…It is also clear that neutrophils will rarely, if ever, be exposed to a single class of agonists in vitro and that the extracellular environment and the extracellular matrix play major roles in directing and redirecting neutrophil responses (including the control of transcriptional programmes [171]). This is intimately related to the development of neutrophil subtypes and activated phenotypes that are likely to be encountered at inflammatory and tumor sites [172,173].…”