The Role of Macrophages in the Biological Reaction to Wear Debris from Artificial Joints.

Normal usage of total joint replacements results in the production of wear debris and other byproducts. In particular, polyethylene particles are heavily involved in the stimulation of local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone resorption (osteolysis), and eventually implant loosening. As sentinels of the innate immune system, cells of the monocyte/macrophage lineage initiate the inflammatory cascade that lead to osteolysis.

Differentially Expressed in Chondrocytes 2 (DEC2) Increases the Expression of IL-1β and Is Abundantly Present in Synovial Membrane in Rheumatoid Arthritis.

Objective: Patients with rheumatoid arthritis (RA) have altered circadian rhythm of circulating serum cortisol, melatonin and IL-6, as well as disturbance in the expression of clock genes ARNTL2 and NPAS2. In humans, TNFα increases the expression ARNTL2 and NPAS2 but paradoxically suppresses clock output genes DPB and PER3. Our objective was to investigate the expression of direct clock suppressors DEC1 and DEC2 (BHLHE 40 and 41 proteins) in response to TNFα and investigate their role during inflammation.

Soluble biglycan: a potential mediator of cartilage degradation in osteoarthritis.

Background: Soluble biglycan (sBGN) and soluble decorin (sDCN), are two closely related essential components of extracellular matrix which both have been shown to possess proinflammatory properties. We studied whether sBGN or sDCN were present in synovial fluid (SF) of osteoarthritis (OA) or rheumatoid arthritis (RA) patients and studied sBGN or sDCN potential role in the degradation of OA cartilage.

Methods: SF obtained from meniscus tear, OA, and RA patients were analysed for sBGN and sDCN using enzyme-linked immunosorbent assays.

Establishment of Green Fluorescent Protein and Firefly Luciferase Expressing Mouse Primary Macrophages for In Vivo Bioluminescence Imaging.

Macrophages play a key role in tissue homeostasis as well as in a range of pathological conditions including atherosclerosis, cancer, and autoimmunity. Many aspects of their in vivo behavior are, however, poorly understood. Bioluminescence imaging (BLI) with green fluorescent protein (GFP) and firefly luciferase (FLUC) labelled autologous reporter macrophages could potentially offer a powerful tool to study macrophage biology, but this approach has been hindered by the relative difficulty of efficient gene transfer into primary macrophages.

Effects of S53P4 bioactive glass on osteoblastic cell and biomaterial surface interaction.

To study the effect of bioactive glass bone substitute granules (S53P4) and hypoxic atmospheric conditions on human osteoblastic cell adhesion on different biomaterials. Cellular adhesion and cytoskeletal organization were studied on titanium, polytetrafluoroethylene, polydimethylsiloxane and S53P4 plates in the presence or absence of S53P4 granules. Cells used were human osteoblast-like SaOS-2 cells.

Effect of S53P4 bone substitute on staphylococcal adhesion and biofilm formation on other implant materials in normal and hypoxic conditions.

To study the effect of bioactive glass bone substitute granules (S53P4) on bacterial adhesion and biofilm formation on other simultaneously used implant materials and the role of the hypoxic conditions to the adhesion. Bacterial and biofilm formation were studied on materials used both in middle ear prostheses and in fracture fixtures (titanium, polytetrafluoroethylene, polydimethylsiloxane and bioactive glass plates) in the presence or absence of S53P4 granules. The experiments were done either in normal atmosphere or in hypoxia simulating atmospheric conditions of middle ear, mastoid cavity and sinuses.

Diminished salivary epidermal growth factor secretion: a link between Sjögren's syndrome and autoimmune gastritis?

Objectives: Healthy human labial salivary glands produce epidermal growth factor (EGF). In Sjögren's syndrome (SS), EGF staining is diminished. SS is also associated with chronic autoimmune corpus gastritis.

Osteogenic differentiation of mesenchymal stromal cells in two-dimensional and three-dimensional cultures without animal serum.

Introduction: Bone marrow-derived mesenchymal stromal cells (MSCs) have been intensely studied for the purpose of developing solutions for clinical tissue engineering. Autologous MSCs can potentially be used to replace tissue defects, but the procedure also carries risks such as immunization and xenogeneic infection. Replacement of the commonly used fetal calf serum (FCS) with human platelet lysate and plasma (PLP) to support cell growth may reduce some of these risks.

A bioactive hybrid three-dimensional tissue-engineering construct for cartilage repair.

The aim was to develop a hybrid three-dimensional-tissue engineering construct for chondrogenesis. The hypothesis was that they support chondrogenesis. A biodegradable, highly porous polycaprolactone-grate was produced by solid freeform fabrication.

Distinctive expression pattern of interleukin-17 cytokine family members in colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers in both genders. Even though interleukin (IL)-17A was shown to play an important role in intestinal tumourigenesis and CRC, other IL-17 family members were not studied well. We therefore studied the expression of IL-17 cytokine family members in CRC.

Autoinflammation Around AES Total Ankle Replacement Implants.

Background: Failure of total ankle replacement (TAR) can be characterized by early peri-implant osteolysis even in the presence of very modest numbers of wear particles. The hypothesis of the study was that this reaction is in part mediated by autoinflammatory responses mediated via damage-associated molecular patterns (DAMPs, danger signals) and pattern-recognizing danger signal receptors (PRRs).

Methods: Peri-implant tissue and control samples from 10 patients with AES implants were immunostained for hypoxia inducible factor-1α (HIF-1α), activated caspase-3, high-mobility group box 1 (HMGB1), receptor for advanced glycation end product (RAGE), and toll-like receptors TLR2 and TLR4.

Epithelial Cell Apoptosis in Recurrent Aphthous Ulcers.

A recurrent aphthous ulcer (RAU) is a common inflammatory ulcerative lesion affecting oral mucosa. We studied the eventual apoptosis of epithelial cells from the point of view of ulcer and inflammation. RAU lesions and healthy mucosa samples were immunostained for caspase-3 and high-mobility group box 1 (HMGB1).

The cost-effectiveness of biologics for the treatment of rheumatoid arthritis: a systematic review.

Background And Objectives: Economic evaluations provide information to aid the optimal utilization of limited healthcare resources. Costs of biologics for Rheumatoid arthritis (RA) are remarkably high, which makes these agents an important target for economic evaluations. This systematic review aims to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically.

Activation of histamine H3 receptor decreased cytoplasmic Ca(2+) imaging during electrical stimulation in the skeletal myotubes.

Histamine is a neurotransmitter and chemical mediator in multiple physiological processes. Histamine H3 receptor is expressed in the nervous system, heart, and gastrointestinal tract; however, little is known about H3 receptor in skeletal muscle. The aim of this study was to investigate the role of H3 receptor in skeletal myotubes.

Human beta-defensin-3 producing cells in septic implant loosening.

Human β-defensin-3 (hBD-3) has been found in synovial fluid and later in periprosthetic tissues in septic joint implant loosening. The aim of the present study was to identify its cellular sources. Tissue samples from 12 patients were analyzed.

Rates of serious infections and malignancies among patients with rheumatoid arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy.

Objective: Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy.

Methods: The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users.

Identification of histamine receptor subtypes in skeletal myogenesis.

To date, conventional and/or novel histamine receptors (HRs) have not been investigated in mouse skeletal myogenesis. Therefore, the present study aimed to investigate the HR‑subtypes in skeletal myogenesis. The myogenesis of C2C12 skeletal myoblasts was evaluated using desmin, myogenin and myosin heavy chain (Myh) as early, intermediate and late differentiation markers, respectively.

Identification of Sjögren's syndrome oral fluid biomarker candidates following high-abundance protein depletion.

Objective: SS is an autoimmune exocrinopathy affecting ∼1 million patients in the USA that is diagnosed mostly in middle-aged women. Oral fluids (OFs) serving as the mirror of the body were suggested as an ideal non-invasive diagnostic tool. Previously we developed depletion techniques for OF high-abundance proteins to increase visualization of low-abundance proteins.

Valsalva leak point pressure-associated Q-tip angle and simple female stress urinary incontinence symptoms.

Purpose: To clarify the association between clinically defined simple stress urinary incontinence (SUI) symptoms and urodynamic SUI, we examined the relationship between Valsalva leak point pressure (VLPP) as measured by the Q-tip test and Stamey grade in simple female SUI.

Methods: Two hundred grade I or II female SUI patients with SUI symptom were examined by reviewing medical history; physical examination; urethral mobility as assessed by Q-tip test; stress test; and cystometry, including VLPP measurement. On the basis of the VLPP, patients were classified into urethral hypermobility [UH, subdivided into anatomical incontinence (AI) and equivocal incontinence (EI)] or intrinsic sphincter deficiency groups for analysis of the relationship between VLPP and Stamey grade and Q-tip angle.

Histamine H4 receptor in oral lichen planus.

Objectives: Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4 Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines.

Materials And Methods: Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes.

Sjögren's syndome and extragonadal sex steroid formation: a clue to a better disease control?

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphoplasmacytoid focal adenitis leading to mucosal dryness, with 9:1 female dominance and peak incidence at menopause. Due to autoimmune adenitis it can be speculated that the normal epithelial cell renewal has failed, possibly as a result of local intracrine failure to process dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). Local intracrine/-cellular DHT deficiency seems to predispose to SS if estrogens are low, in menopausal women and in men.

Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps.

Modulation of macrophage polarization is emerging as promising means to mitigate wear particle-induced inflammation and periprosthetic osteolysis. As a model for continuous local drug delivery, we used miniature osmotic pumps to deliver IL-4 in order to modulate macrophage polarization in vitro from nonactivated M0 and inflammatory M1 phenotypes towards a tissue regenerative M2 phenotype. Pumps delivered IL-4 into vials containing mouse bone marrow macrophage (mBMM) media.

Characterization of macrophage polarizing cytokines in the aseptic loosening of total hip replacements.

Aseptic loosening of hip replacements is driven by the macrophage reaction to wear particles. The extent of particle-induced macrophage activation is dependent on the state of macrophage polarization, which is dictated by the local cytokine microenvironment. The aim of the study was to characterize cytokine microenvironment surrounding failed, loose hip replacements with an emphasis on identification of cytokines that regulate macrophage polarization.

Increased beta 2 defensin in recurrent aphthous ulcer.

Objectives: It was hypothesized that beta 2 defensin (BD-2) is increased in RAU lesions compared with healthy controls to promote anti-microbial host defence.

Methods: RAU and control mucosa samples were subjected to quantitative real-time PCR and immunostained for BD-2, CD68, mast cell tryptase and 4-hydroxynonenal (4HNE). The effect of tumour necrosis factor-α (TNF-α) ± interleukin-17C (IL-17C), without and with vitamin K3, was studied on BD-2 expression in epithelial SCC-25 cells.