Human Osteoarthritic Chondrocytes Express Nineteen Different TRP-Genes-TRPA1 and TRPM8 as Potential Drug Targets.

Transient receptor potential (TRP) ion channels are expressed in neuronal and some non-neuronal cells and are involved particularly in pain and thermosensation. We previously showed that TRPA1 is functionally expressed in human osteoarthritic (OA) chondrocytes and mediates inflammation, cartilage degradation, and pain in monosodium-iodoacetate-induced experimental OA. In the present study, we explored the expression of TRP-channels in primary human OA chondrocytes and investigated whether drugs used in the treatment of OA, ibuprofen and glucocorticoids, have effects on TRP-channel expression.

Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1.

Mitogen-activated protein kinase phosphatase-1 (MKP-1) is upregulated in inflammation and reduces the activity of proinflammatory mitogen-activated protein kinases (MAP kinases) by dephosphorylation. MAP kinases are intracellular signaling pathways that mediate the cellular effects of proinflammatory cytokines. In the present study, we investigated the effects of the glucocorticoid dexamethasone on the expression of catabolic enzymes in chondrocytes and tested the hypothesis that these effects are mediated through MKP-1.

Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central T1/T2/T17 Cytokines.

Chronic low-grade inflammation plays a central role in the pathogenesis of osteoarthritis (OA), and several pro- and anti-inflammatory cytokines have been implicated to mediate and regulate this process. Out of these cytokines, particularly IFNγ, IL-1β, IL-4 and IL-17 are associated with different phenotypes of T helper (T) cells and macrophages, both examples of cells known for great phenotypic and functional heterogeneity. Chondrocytes also display various phenotypic changes during the course of arthritis.

Effects of ibuprofen on gene expression in chondrocytes from patients with osteoarthritis as determined by RNA-Seq.

Non-steroidal anti-inflammatory drugs are a widely used symptomatic treatment in osteoarthritis (OA), but their effects on cartilage remain controversial. We studied the effects of ibuprofen on gene expression in chondrocytes from patients with OA using RNA-Seq. Chondrocytes were isolated from cartilage samples of patients with OA undergoing knee replacement surgery, cultured with ibuprofen, and total mRNA was sequenced.

Is the Preoperative Use of Antidepressants and Benzodiazepines Associated with Opioid and Other Analgesic Use After Hip and Knee Arthroplasty?

Background: Mental health disorders can occur in patients with pain conditions, and there have been reports of an increased risk of persistent pain after THA and TKA among patients who have psychological distress. Persistent pain may result in the prolonged consumption of opioids and other analgesics, which may expose patients to adverse drug events and narcotic habituation or addiction. However, the degree to which preoperative use of antidepressants or benzodiazepines is associated with prolonged analgesic use after surgery is not well quantified.

Widespread regulation of gene expression by glucocorticoids in chondrocytes from patients with osteoarthritis as determined by RNA-Seq.

Background: Intra-articular glucocorticoid (GC) injections are widely used as a symptomatic treatment for osteoarthritis (OA). However, there are also concerns about their potentially harmful effects, and their detailed effects on chondrocyte phenotype remain poorly understood.

Methods: We studied the effects of dexamethasone on gene expression in OA chondrocytes with RNA-Seq.

Regulation of gene expression by MF63, a selective inhibitor of microsomal PGE synthase 1 (mPGES1) in human osteoarthritic chondrocytes.

Background And Purpose: mPGES1 catalyses the production of PGE , the most abundant prostanoid related to inflammation and pain in arthritis. mPGES1 is suggested to be a safer and more selective drug target in inflammatory conditions compared to the COX enzymes inhibited by NSAIDs. In the present study, we investigated the effects of the selective mPGES1 inhibitor MF63 on gene expression in primary human chondrocytes from patients with osteoarthritis (OA).

Predictors of the use of analgesic drugs 1 year after joint replacement: a single-center analysis of 13,000 hip and knee replacements.

Background: Pain persists in a moderate number of patients following hip or knee replacement surgery. Persistent pain may subsequently lead to the prolonged consumption of analgesics after surgery and expose patients to the adverse drug events of opioids and NSAIDs, especially in older patients and patients with comorbidities. This study aimed to identify risk factors for the increased use of opioids and other analgesics 1 year after surgery and focused on comorbidities and surgery-related factors.

Novel adipokine associated with OA: retinol binding protein 4 (RBP4) is produced by cartilage and is correlated with MMPs in osteoarthritis patients.

Objective: Retinol binding protein 4 (RBP4) is a member of the lipocalin family and a vitamin A carrier in the blood. More recently, RBP4 has been described as an adipokine that is involved in insulin resistance and metabolic syndrome (MetS). As obesity, MetS and some adipokines contribute to the pathogenesis of osteoarthritis (OA), we investigated RBP4 in patients with OA.

Use of prescription analgesic drugs before and after hip or knee replacement in patients with osteoarthritis.

Background: Analgesic drugs are recommended to treat pain caused by osteoarthritis, and joint replacement should decrease the need for them. We aimed to determine the user rates of analgesic drugs before and after joint replacement.

Methods: All patients who underwent a primary hip or knee replacement for osteoarthritis from 2002 to 2013 in a region of 0.

Downregulation of microsomal prostaglandin E synthase-1 (mPGES-1) expression in chondrocytes is regulated by MAP kinase phosphatase-1 (MKP-1).

Objectives: Microsomal prostaglandin E synthase-1 (mPGES-1) catalyses the formation of PGE in inflammatory tissues. It is considered a potential drug target in inflammatory conditions to achieve clinical benefits comparable to NSAIDs with a better tolerability. Inhibitors of mPGES-1 are under development but the pharmacological regulation of mPGES-1 expression remains poorly known.

IL-6 in Osteoarthritis: Effects of Pine Stilbenoids.

Interleukin-6 (IL-6) is involved in the pathogenesis of various inflammatory diseases, like rheumatoid arthritis (RA). In the present study, we investigated the role of IL-6 in osteoarthritis (OA) patients and the effects of the stilbenoids monomethyl pinosylvin and pinosylvin on the expression of the cartilage matrix components aggrecan and collagen II and the inflammatory cytokine IL-6 in human OA chondrocytes. Synovial fluid and plasma samples were obtained from 100 patients with severe OA [BMI 29.

Gene expression in adverse reaction to metal debris around metal-on-metal arthroplasty: An RNA-Seq-based study.

Joint replacement surgery is a standard treatment of advanced osteoarthritis (OA). Since 2000, cobalt-chromium (CoCr) metal-on-metal (MoM) implants were widely used in hip arthroplasties. Some patients developed "adverse reaction to metal debris" (ARMD) around the prosthesis, resulting in a need for revision surgery.

Catabolic and proinflammatory effects of leptin in chondrocytes are regulated by suppressor of cytokine signaling-3.

Background: Previous studies provide evidence that adipokine leptin increases production of catabolic and proinflammatory factors in chondrocytes and serves as a link between obesity and osteoarthritis (OA). However, the magnitude of the response to leptin treatment varies greatly between chondrocytes from different donor patients. In the present study, we investigated the regulatory role of suppressor of cytokine signaling-3 (SOCS-3) in the leptin-induced responses in OA cartilage.

Factors Associated With Trunnionosis in the Metal-on-Metal Pinnacle Hip.

Background: Trunnionosis of the tapered head-stem junction of total hip arthroplasties, either through corrosion or mechanical wear, has been implicated in early implant failure. Retrieval analysis of large numbers of failed implants can help us better understand the factors that influence damage at this interface.

Methods: In this study, we examined 120 retrieved total hip arthroplasties of one bearing design, the 36-mm diameter metal-on-metal, DePuy Pinnacle, that had been paired with 3 different stems.

The Inflammatory Phenotype in Failed Metal-On-Metal Hip Arthroplasty Correlates with Blood Metal Concentrations.

Introduction: Hip arthroplasty is the standard treatment of a painful hip destruction. The use of modern metal-on-metal (MOM) bearing surfaces gained popularity in total hip arthroplasties during the last decade. Recently, worrisome failures due to adverse reaction to metal debris (ARMD), including pseudotumor response, have been widely reported.

Higher Blood Cobalt and Chromium Levels in Patients With Unilateral Metal-on-Metal Total Hip Arthroplasties Compared to Hip Resurfacings.

Background: Adverse soft tissue reactions in metal-on-metal (MoM) hip replacements are associated with cobalt (Co) and chromium (Cr) ions in blood. We report the prevalence and risk factors for elevated blood Co and Cr levels in patients with a unilateral MoM hip.

Methods: From a single institution, blood Co and Cr levels were analyzed in 1748 patients (692 hip resurfacings and 1056 total hip arthroplasties [THAs]).

Diabetes is associated with persistent pain after hip and knee replacement.

Background And Purpose: In some patients, for unknown reasons pain persists after joint replacement, especially in the knee. We determined the prevalence of persistent pain following primary hip or knee replacement and its association with disorders of glucose metabolism, metabolic syndrome (MetS), and obesity.

Patients And Methods: The incidence of pain in the operated joint was surveyed 1-2 years after primary hip replacement (74 patients (4 bilateral)) or primary knee replacement (119 patients (19 bilateral)) in 193 osteoarthritis patients who had participated in a prospective study on perioperative hyperglycemia.

Functional gain following knee replacement in patients aged 75 and older: a prospective follow-up study.

Background And Aims: The aim of this prospective follow-up study was to analyze which patient characteristics predict better functional ability, as well as improvement in the ability, following knee replacement in the aged. The focus was on the impact of specific comorbidities and radiologic data.

Methods: Knee osteoarthritis patients aged ≥75 years (n = 167) scheduled for knee replacement answered to a questionnaire asking about performance in the activities of daily living (ADL) before the operation, and 1 year afterwards.

Risk factors for perioperative hyperglycemia in primary hip and knee replacements.

Background And Purpose: Perioperative hyperglycemia has been associated with adverse outcomes in several fields of surgery. In this observational study, we identified factors associated with an increased risk of hyperglycemia following hip and knee replacement.

Patients And Methods: We prospectively monitored changes in glucose following primary hip and knee replacements in 191 patients with osteoarthritis.

Single periarticular local infiltration analgesia reduces opiate consumption until 48 hours after total knee arthroplasty. A randomized placebo-controlled trial involving 56 patients.

Background: Randomized trials evaluating efficacy of local infiltration analgesia (LIA) have been published but many of these lack standardized analgesics. There is a paucity of reports on the effects of LIA on functional capability and quality of life.

Methods: 56 patients undergoing unilateral total knee arthroplasty (TKA) were randomized into 2 groups in this placebo-controlled study with 12-month follow-up.