Proteoglycan 4 (Lubricin) and regulation of xanthine oxidase in synovial macrophage as a mechanism of controlling synovitis.

Background: Synovial macrophages (SMs) are important effectors of joint health and disease. A novel Cx3CR1 + TREM2 + SM population expressing the tight junction protein claudin-5, was recently discovered in synovial lining. Ablation of these SMs was associated with onset of arthritis.

Protein phosphatase 2A regulates xanthine oxidase-derived ROS production in macrophages and influx of inflammatory monocytes in a murine gout model.

Gout is a common arthritis, due to deposition of monosodium urate (MSU) crystals which results in IL-1β secretion by tissue-resident macrophages. Xanthine oxidase (XO) catalyzes uric acid (UA) production and in the process, reactive oxygen species (ROS) are generated which contributes to NLRP3 inflammasome activation. Protein phosphatase 2A (PP2A) may be involved in regulating inflammatory pathways in macrophages.

Exploratory Analysis of Outpatient Visits for US Adults Diagnosed with Lupus Erythematosus: Findings from the National Ambulatory Medical Care Survey 2006-2016.

The study aims to assess office-based visit trends for lupus patients and evaluate their medication burden, chronic conditions, and comorbidities. This cross-sectional study used data from the National Ambulatory Medical Care Survey (NAMCS), a survey sample weighted to represent national estimates of outpatient visits. Adult patients diagnosed with lupus were included.

Quadruped Gait and Regulation of Apoptotic Factors in Tibiofemoral Joints following Intra-Articular rhPRG4 Injection in Null Mice.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4-PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4).

Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation of Monocytes and Reduces IL-1β Secretion by Urate Crystal Stimulated Gout PBMCs.

Objectives: To compare phagocytic activities of monocytes in peripheral blood mononuclear cells (PBMCs) from acute gout patients and normal subjects, examine monosodium urate monohydrate (MSU) crystal-induced IL-1β secretion ± recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes.

Methods: Acute gout PBMCs were collected from patients in the Emergency Department and normal PBMCs were obtained from a commercial source. Monocytes in PBMCs were identified by flow cytometry.

Proteoglycan-4 is an essential regulator of synovial macrophage polarization and inflammatory macrophage joint infiltration.

Background: Synovial macrophages perform a multitude of functions that include clearance of cell debris and foreign bodies, tissue immune surveillance, and resolution of inflammation. The functional diversity of macrophages is enabled by distinct subpopulations that express unique surface markers. Proteoglycan-4 (PRG4) is an important regulator of synovial hyperplasia and fibrotic remodeling, and the involvement of macrophages in PRG4's synovial role is yet to be defined.

Fingolimod Phosphate (FTY720-P) Activates Protein Phosphatase 2A in Human Monocytes and Inhibits Monosodium Urate Crystal-Induced Interleukin-1 Production.

Gout is a chronic inflammatory arthritis caused by monosodium urate monohydrate (MSU) crystal deposits in joints of lower limbs. Phagocytic uptake of MSU crystals by joint-resident macrophages and recruited circulating monocytes results in IL-1 expression and production. Current acute gout treatments have serious toxicities and suffer suboptimal clinical outcomes.

Recombinant Human Proteoglycan-4 Mediates Interleukin-6 Response in Both Human and Mouse Endothelial Cells Induced Into a Sepsis Phenotype.

Objectives: Sepsis is a leading cause of death in the United States. Putative targets to prevent systemic inflammatory response syndrome include antagonism of toll-like receptors 2 and 4 and CD44 receptors in vascular endothelial cells. Proteoglycan-4 is a mucinous glycoprotein that interacts with CD44 and toll-like receptor 4 resulting in a blockade of the NOD-like receptor pyrin domain-containing-3 pathway.

Proteoglycan-4 regulates fibroblast to myofibroblast transition and expression of fibrotic genes in the synovium.

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor.

CD44 Receptor Mediates Urate Crystal Phagocytosis by Macrophages and Regulates Inflammation in A Murine Peritoneal Model of Acute Gout.

Gout is a chronic arthritis caused by the deposition of poorly soluble monosodium urate monohydrate (MSU) crystals in peripheral joints. Resident macrophages initiate inflammation in response to MSU mediated by NF-κB nuclear translocation and NLRP3 inflammasome activation. We investigated the role of CD44, a transmembrane receptor, in mediating MSU phagocytosis by macrophages.

Design and Biological Evaluation of Colchicine-CD44-Targeted Peptide Conjugate in an In Vitro Model of Crystal Induced Inflammation.

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity.

Two compartment pharmacokinetic model describes the intra-articular delivery and retention of rhprg4 following ACL transection in the Yucatan mini pig.

Treatment of the injured joint with rhPRG4 is based on recent observations that inflammation diminishes expression of native PRG4. Re-establishing lubrication between pressurized and sliding cartilage surfaces during locomotion promotes the nascent expression of PRG4 and thus intra-articular (IA) treatment strategies should be supported by pharmacokinetic evidence establishing the residence time of rhPRG4. A total of 21 Yucatan minipigs weighing ∼55 kg each received 4 mg of I-rhPRG4 delivered by IA injection 5 days following surgical ACL transection.

Recombinant human proteoglycan-4 reduces phagocytosis of urate crystals and downstream nuclear factor kappa B and inflammasome activation and production of cytokines and chemokines in human and murine macrophages.

Background: Gout is an inflammatory arthritis caused by monosodium urate monohydrate (MSU) crystals' joint deposition. MSU phagocytosis by resident macrophages is a key step in gout pathogenesis. MSU phagocytosis triggers nuclear factor kappa B (NFκB) activation and production of cytokines and chemokines.

cAMP attenuates TGF-β's profibrotic responses in osteoarthritic synoviocytes: involvement of hyaluronan and PRG4.

Osteoarthritis (OA) is characterized by synovitis and synovial fibrosis. Synoviocytes are fibroblast-like resident cells of the synovium that are activated by transforming growth factor (TGF)-β to proliferate, migrate, and produce extracellular matrix. Synoviocytes secrete hyaluronan (HA) and proteoglycan-4 (PRG4).

Outcomes of a pharmacist-managed clinic for underserved persons with unmanaged type 2 diabetes mellitus.

Background: A multidisciplinary approach is recommended for the management of type 2 diabetes mellitus (DM).

Aim: To evaluate the impact of a pharmacist intervention on haemoglobin A1c (HbA), systolic blood pressure (SBP), diastolic blood pressure (DBP), and diabetes-related hospitalisations in an underserved cohort with unmanaged type 2 DM.

Methods: This analysis was a retrospective cohort study.

Role of CD44 in Regulating TLR2 Activation of Human Macrophages and Downstream Expression of Proinflammatory Cytokines.

Osteoarthritis (OA) is a low-grade chronic inflammatory joint disease. Innate immunity contributes to OA progression, mediated by TLR2 and TLR4. We evaluated the role of cluster determinant 44 (CD44), a transmembrane glycoprotein, in regulating TLR2-linked macrophage activation and resultant proinflammatory responses.

The autocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes.

Background: Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation.

Intra-articular interleukin-1 receptor antagonist (IL1-ra) microspheres for posttraumatic osteoarthritis: in vitro biological activity and in vivo disease modifying effect.

Background: Interleukin-1 receptor antagonist (IL-1 ra) can be disease-modifying in posttraumatic osteoarthritis (PTOA). One limitation is its short joint residence time. We hypothesized that IL-1 ra encapsulation in poly (lactide-co-glycolide) (PLGA) microspheres reduces IL-1 ra systemic absorption and provides an enhanced anti-PTOA effect.

Reduction of friction by recombinant human proteoglycan 4 in IL-1α stimulated bovine cartilage explants.

A boundary lubricant attaches and protects sliding bearing surfaces by preventing interlocking asperity-asperity contact. Proteoglycan-4 (PRG4) is a boundary lubricant found in the synovial fluid that provides chondroprotection to articular surfaces. Inflammation of the diarthrodial joint modulates local PRG4 concentration.

The interaction of lubricin/proteoglycan 4 (PRG4) with toll-like receptors 2 and 4: an anti-inflammatory role of PRG4 in synovial fluid.

Background: Lubricin/proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 has a homeostatic multifaceted role in the joint. PRG4 intra-articular treatment retards progression of cartilage degeneration in pre-clinical posttraumatic osteoarthritis models.

Achieving blood pressure control among renal transplant recipients by integrating electronic health technology and clinical pharmacy services.

Purpose: The implementation and outcomes of a program combining electronic home blood pressure monitoring (HBPM) and pharmacist-provided medication therapy management (MTM) services in a renal transplantation clinic are described.

Summary: Patients enrolled in the program were provided with a computer-enabled blood pressure monitor. A dedicated renal transplantation pharmacist was integrated into the renal transplantation team under a collaborative care practice agreement.

Chemotherapy e-prescribing: opportunities and challenges.

Chemotherapy drugs are characterized by low therapeutic indices and significant toxicities at clinically prescribed doses, raising serious issues of drug safety. The safety of the chemotherapy medication use process is further challenged by regimen complexity and need to tailor treatment to patient status. Errors that occur during chemotherapy prescribing are associated with serious and life-threatening outcomes.

Lubricin/Proteoglycan 4 Binding to CD44 Receptor: A Mechanism of the Suppression of Proinflammatory Cytokine-Induced Synoviocyte Proliferation by Lubricin.

Objective: To evaluate the binding of recombinant human proteoglycan 4 (rhPRG4) to CD44 receptor and its consequences on cytokine-induced synoviocyte proliferation.

Methods: The binding of rhPRG4 to CD44 and competition with high molecular weight (HMW) hyaluronic acid (HA) was evaluated using a direct enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance. Sialidase A and O-glycosidase digestion of rhPRG4 was performed, and CD44 binding was evaluated using ELISA.