Pathways of cell activation in spondyloarthropathies

Abstract

The initiating event in cell activation is unknown in most autoimmune diseases. The role of infection is clear in some cases, especially in reactive arthritis; however, there is little evidence of a specific organism in other spondyloarthropathies. Common pathways of cell-cell interaction and activation manifest in inflammation, but subtle differences may exist. The presence of T cells, macrophages, and B-lymphocytes suggest an autoimmune mechanism; the arthritogenic peptide theory has been proposed. Furthermore, the association of spondyloarthropathies with HLA-B27 suggests it may be important in synovial T-cell activation. Other cell types involved in the process of bone and cartilage destruction, including fibroblasts and osteoclasts, may also be activated. Endothelial activation and angiogenesis may be a critical primary event in these diseases. Finally, trauma (physical or psychological) in the form of stress may be an important factor; the nervous system and neuropeptides may play a role in cell activation and initiation of arthritis.

Notch‐1 mediates endothelial cell activation and invasion in psoriasis

“…Targeted disruption of Notch signalling components can result in embryonic lethality, defects in angiogenic vascular remodelling, abnormalities in vessel structure, branching and patterning and dysfunctional vascular tip versus stalk cell development (42)(43)(44). Furthermore, Notch signalling is known to mediate the functional effects of many pro-angiogenic molecules, such as VEGF, PDGF-B and Ang1/2, which are known to be associated with determining the distinct vascular morphology observed in psoriasis and PsA (6)(7)(8). We have previously demonstrated in the same cohort an increase in vessel density and in the expression of key angiogenic factors, specifically CD31, VEGF and Ang2 in lesional versus non-lesional skin (6).…”

“…Previous studies have shown that microvessels of the papillary dermis are elongated, tortuous and dilated with increased endothelial cell (EC) proliferation (3,4) and changes similar to the distinct vascular morphology were observed in early psoriatic arthritis (PsA) joints (5). This hypervascularized state is highly associated with increased expression of pro-angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietins (Ang), placental growth factor (PlGF), platelet-derived growth factor (PDGF), platelet endothelial cell adhesion molecule (PECAM) and podoplanin (6)(7)(8)(9)(10). Interactions between angiogenic growth factors are critical for EC survival/anti-apoptotic signalling pathways, which preserve the integrity of the newly formed vessel.…”

Bone Vascularization in Normal and Disease Conditions

“…These are: avascular necrosis, pachydermoperiostosis, osteopetrosis, rickets, osteoporosis, inflammatory bone loss, multiple myeloma, Paget’s disease, metastatic bone disease, melorheostosis, Gorham–Stout disease (GSD), Klippel–Trénaunay syndrome (KTS), and vertebral angiomatosis (4–6, 52–79). Most of these conditions are related to a defect of vascular supply, although a few phenotypes are caused by an excessive vascularization (Table 1).…”

Vascular Biology and the Skeleton

“…Abundant evidence indicates that the vasculature plays an active and important role in numerous skeletal pathologies, from vascular necrosis, ( 155–157 ) to pachydermoperiostosis, ( 158–161 ) osteopetrosis, ( 162–165 ) rickets, ( 62–64 , 166–171 ) osteoporosis, ( 31–33 ) inflammatory bone loss, ( 138 , 141 , 142 , 172–178 ) multiple myeloma, ( 179–182 ) Paget's disease of bone, ( 183 ) metastatic bone disease, ( 19 , 29 , 30 , 184 ) melorheostosis, ( 185 ) and Gorham‐Stout disease. ( 186 ) In such cases, pathological perturbations in the normal bone vasculature are associated (in a correlative or causative fashion) with profound changes in skeletal physiology.…”

“…For example, angiogenesis is a prime factor underlying the pathology of various diseases of inflammatory bone loss, including rheumatoid arthritis and periodontal disease. ( 172–178 ) Unlike normal bone healing, in which angiogenesis (and inflammation) is appropriately stimulated and then halted, angiogenesis is persistently induced in chronic inflammatory conditions, leading to excessive recruitment of inflammatory cells, including osteoclast precursors, that engage in cartilage erosion and bone destruction. ( 138 , 175 ) Because angiogenesis and inflammation behave as codependent reciprocal regulators of one another, inhibitors of either process produce beneficial effects to dampen the other as well.…”