Article ; Online: Evidence in support of the bone marrow as the primary lesion in axial spondyloarthritis.
Current opinion in rheumatology
2023 Volume 35, Issue 4, Page(s) 213–218
Abstract: Purpose of review: Over the past several decades, the concept that the primary lesion accounting for the development of axSpA is an enthesopathy has been widely accepted. However, the hallmark abnormality of axSpA occurs in the sacroiliac joint at the ... ...
| Abstract | Purpose of review: Over the past several decades, the concept that the primary lesion accounting for the development of axSpA is an enthesopathy has been widely accepted. However, the hallmark abnormality of axSpA occurs in the sacroiliac joint at the interface of cartilage and bone at a location remote from any anatomical enthesis. Both imaging and histopathological data from the sacroiliac joint point to immunopathogenetic events in the bone marrow as being of primary importance. Here, we discuss new developments in our understanding of immune events in the bone marrow relevant to axSpA that reinforce the need for a change in our conceptual paradigm for the pathogenesis of axSpA. Recent findings: Human spinal enthesis samples contain myeloperoxidase-expressing cells, a marker of neutrophils, and mucosal-associated invariant T cells in the perientheseal bone marrow, which may be activated by stromal cells and circulating microbial products to express IL-17A and IL-17F and tumor necrosis factor (TNF). Evaluation of transcriptomes of monocytes from patients with axSpA demonstrates a lipopolysaccharide/TNF signature characterized by the expression of genes associated with granulocytopoietic bone marrow cells. This neutrophil-like phenotype is more evident in established and more severe axSpA and may be activated by microbial products from the gut. A similar expansion of granulocyte-monocyte progenitor-driven hematopoiesis occurs in the SKG mouse driven by granulocyte-macrophage colony-stimulating factor. Mesenchymal stem cells (MSCs) from ankylosing spondylitis patients are more likely to exhibit osteogenic differentiation than MSCs from healthy donors, which may be mediated by the formation of specific clusters of transcriptional factors, super enhancers, regulated by axSpA-associated single nucleotide polymorphisms located mostly in noncoding regions. TNF-α may enhance directional migration of AS-MSC compared with MSC from healthy controls from the bone marrow to entheseal soft tissue, which is mediated by increased expression of engulfment and cell motility protein 1 (ELMO1). TNF and IL-17A display differential effects on adipogenesis and osteogenesis of MSC in perientheseal bone marrow and soft tissue. Summary: Bone marrow has the capacity to undergo rapid adaptation in terms of cell composition, differentiation, and immune function, resulting in inflammation and osteogenesis in axSpA. |
|---|---|
| MeSH term(s) | Humans ; Animals ; Mice ; Interleukin-17/metabolism ; Bone Marrow ; Osteogenesis ; Spondylitis, Ankylosing/metabolism ; Cell Differentiation ; Tumor Necrosis Factor-alpha ; Spondylarthritis ; Adaptor Proteins, Signal Transducing/metabolism |
| Chemical Substances | Interleukin-17 ; Tumor Necrosis Factor-alpha ; ELMO1 protein, mouse ; Adaptor Proteins, Signal Transducing |
| Language | English |
| Publishing date | 2023-04-27 |
| Publishing country | United States |
| Document type | Review ; Journal Article |
| ZDB-ID | 1045317-9 |
| ISSN | 1531-6963 ; 1040-8711 |
| ISSN (online) | 1531-6963 |
| ISSN | 1040-8711 |
| DOI | 10.1097/BOR.0000000000000945 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 3028: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.