Inês P. Perpétuo

Imperial College London | Imperial · Postdoc and Fellows Development Centre

Objective . Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TN...

Introduction Ankylosing spondylitis (AS) is typically characterized by focal bone overgrowth and also by systemic bone loss. We hypothesize that the increased osteoproliferation found in AS might be partially due to reduced ability of osteoclast precursors (OCPs) to differentiate into osteoclasts (OCs). Therefore, our aim was to characterize bone r...

Introduction: Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi)...

Our aim was to compare bone gene expression in rheumatoid arthritis (RA) and primary osteoporosis (OP) patients. Secondary aims were to determine the association of gene expression of the Wnt/β-catenin signaling pathway with inflammatory cytokines in the bone microenvironment and to assess the serum levels of Wnt/β-catenin proteins in both groups....

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregu...

Background Our understanding of the biology of osteoblasts is important as they underpin bone remodelling, fracture healing and processes such as osseointegration. Osteoblasts isolated from human humeral samples display distinctive biological activity in vitro, which relates to the samples’ bone types (subchondral (S), trabecular (T), cortical (C))...

This chapter describes the isolation, culture, and staining of osteoblasts. The key advantages of this assay are that it allows direct measurement of bone matrix deposition and mineralization, as well as yielding good quantities of osteoblasts at defined stages of differentiation for molecular and histological analysis. An additional focus of this...

Objective Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that ultimately leads to bone erosions and joint destruction. Methotrexate (MTX) slows bone damage but the mechanism by which it acts is still unknown. In this study, we aimed to assess the effect of MTX and low-dose prednisolone (PDN) on circulating osteoclast...

Background Rheumatoid arthritis (RA) is a systemic, immune mediated inflammatory disease that is associated with bone erosions and joint destruction. Methotrexate (MTX) slows bone damage but the mechanism by which it acts is still unknown. Objectives In this study we aimed to assess the effect of MTX and low dose prednisolone (MTX+PDN) on circulat...

[This corrects the article on p. 5 in vol. 4, PMID: 28191455.].

Primers were designed using primer-BLAST software [19] and adhered to the following specifications: they had to be in an exon-exon junction, at annealing temperature of 60°C, with transcript under 150 bp.

Objective: Effects of bone organ size on isolated osteoblast behaviours are unknown. Exhibiting a hundred-fold range in body mass, inbred canines are an ideal species to determine such relationships. We have therefore undertaken initial studies in both male and female red foxes (Vulpes vulpes), the most abundant and accessible wild canid member in...

Objective: Effects of bone organ size on isolated osteoblast behaviour are unknown. With two orders of magnitude range in body mass, dog breeds are well-suited to determine such relationships. Methods: Femoral heads from three canine hip replacement surgeries were collected. Bone fragments were washed in PBS+AB/AM, trypsin-digested and incubated in...

Hip osteoarthritis is a cause of significant morbidity to people and their canine companions. Medical management is frequently insufficient, leading to surgery to relieve pain and regain mobility. Hip replacements are not without potential complications, including loosening and infection. Currently, there is a focus on uncemented implants to decrea...

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the axial skeleton, characterised by systemic osteoporosis along with new local bone formation. Previous studies have shown that serum levels of TNF, IL-6 and IL-17 are increased in AS patients and may be implicated in the development of secondary osteoporosis, since these c...

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are systemic, immune-mediated diseases. In RA the main target are the peripheral joints while in AS the axial skeleton and enthesis are affected. RA is characterised by bone repair impairment and AS by exaggerated repair, leading to joint ankylosis. The cause for these differences is not yet...

Background The identification of predictive factors of poor response to methotrexate (MTX) in juvenile idiopathic arthritis (JIA) patients could contribute to optimize the treatment strategy, namely by the earlier introduction of biological treatments. Objectives To identify baseline clinical or laboratorial predictive factors of MTX poor response...

Pachydermoperiostosis is a rare clinical entity characterized by skin thickening of the forehead, eyelids, and hands, digital clubbing, and periostosis. Two genes have been associated, HPGD and recently SLCO2A1. We present a detailed clinical and genetic description of an African pachydermoperiostosis patient with a SLCO2A1 mutation. Standard clini...

Background and Objectives Rheumatoid arthritis (RA) is characterised by bone resorption and joint destruction. The receptor activator of NF-kB ligand (RANKL) plays a major role in bone loss because it is responsible for osteoclast differentiation and it is known that hyperactive immune system cells express surface RANKL. Several therapies commonly...

Background Rheumatoid arthritis (RA) and primary osteoporosis (OP) induce bone fragility. In this study we aimed at identifying differences in the mechanisms involved in bone fragility by comparing gene expression between RA and OP bone samples with similar fracture risk factors. Methods Patients with RA submitted to hip replacement surgery were re...

Background: Apolipoprotein E (apoE) gene polymorphisms and undercaboxylated osteocalcin (ucOC) and vitamin K have been associated with fragility fractures and low BMD in general population. The aim of this work was to study whether the effect of apoE gene polymorphisms, seric apoE levels and ucOC influence trabecular bone biomechanics and bone min...

Systemic lupus erythematosus (SLE) patients have lower bone mineral density and increased fracture risk when compared with healthy individuals, due to distinct factors and mechanisms. Bone remodeling is a tightly orchestrated process dependent on several factors, including the balance between receptor activator of nuclear factor κB ligand (RANKL) a...

The polymorphism of the tumor necrosis factor (TNF) promoter gene at position -308 and that of the lymphotoxin alpha (LTA) gene at position 252 have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in some populations. In a nested case-control study, we investigated the possible association of these polymorphisms with...

Fracture healing is orchestrated by a specific set of events that culminates in the repair of bone and reachievement of its biomechanical properties. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the early phases of callus formation in osteoporotic patients. Fifty-s...

Rheumatoid arthritis (RA) is associated with higher levels of inflammatory mediators and with a more atherogenic lipid profile. Dyslipidemia can be present years before arthritis develops. Lymphotoxin-α (LTA) is a cytokine that mediates proinflammatory responses while also participating in lipid homeostasis, and its transcriptional activity is in p...

Background The reasons for the phenotypic differences between spondyloarthritis (SpA) and rheumatoid arthritis (RA) are still unclear. Slight divergences in cytokine networks driving the pathologies might contribute to the distinct clinical manifestations and may represent new treatment opportunities.Objectives The main goal of this work was to com...

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activati...

B cells play an important role in the perpetuation of RA, particularly as autoantibody-producing cells. The ICs that further develop deposit in the joints and aggravate the inflammatory process. However, B-cell contribution in the very early stage of the disease remains unknown. The main goal of this work was to determine the concentration of cytok...

To identify the cytokines that are present at higher levels in the serum and synovial fluid (SF) of patients with established rheumatoid arthritis (RA). Interleukin (IL)1β, IL2, IL4, IL6, IL8, IL10, IL12 (p70), IL17A, IL18, IL22, IL23, interferon (IFN)γ, leptin, MCP-1, MIP-1α, OPG, transforming growth factor β (TGFβ) and …

Rheumatoid arthritis (RA) is a systemic disease characterised by hyperactivation of the immune system and by stimulation of bone resorption by activation of osteoclasts (OC) leading to joint destruction. To assess the activity of OC differentiated from circulating monocytes in patients with RA treated with methotrexate (MTX), anti-tumour necrosis...

Osteoporosis is a systemic skeletal disease characterised by low bone mass, deterioration in microarchitecture, increased bone fragility and susceptibility to fracture. Besides structural properties, biological phenomena driven by differential gene expression could also contribute to the individual diversity of the structural and mechanical propert...

In this study we used a mice model of chronic arthritis to evaluate if bone fragility induced by chronic inflammation is associated with an imbalance in bone turnover and also a disorganization of the bone type I collagen network. Serum, vertebrae and femur bones were collected from eight-month-old polyarthritis SKG mice and controls. Strength of t...