Prescription-grade crystalline glucosamine sulfate as an add-on therapy to conventional treatments in erosive osteoarthritis of the hand: results from a 6-month observational retrospective study.

OBJECTIVE: To evaluate the efficacy of prescription-grade Crystalline Glucosamine Sulfate (pCGS) as an add-on treatment to conventional therapy, compared to usual therapy alone, in patients with erosive osteoarthritis of the hand (EHOA). METHODS: This 6-month retrospective case-control study included patients with concomitant knee osteoarthritis and symptomatic EHOA. Participants were stratified into two groups based on whether or not pCGS (1500 mg/day) was added to the conventional therapy (education and training in ergonomic principles, exercise and use on-demand of symptomatic drugs) for hand osteoarthritis. Patients were evaluated at baseline, after 3 and 6 months. Primary outcomes were the change from baseline to month 6 in Visual Analogue Scale (VAS) hand pain and in Functional Index for Hand Osteoarthritis (FIHOA) score. A set of secondary parameters was also evaluated. RESULTS: 123 patients were included as follows: 67 treated with pCGS in addition to conventional therapy (pCGS Group) and 56 with conventional therapy alone (Control Group). After 6 months a significant difference in VAS and in FIHOA score (p < 0.01 and p < 0.001, respectively) was observed in favor of pCGS Group. Similar results were found for morning stiffness duration (p < 0.05), health assessment questionnaire (p < 0.01) and physical and mental component score of 36-item short form (p < 0.05 and p < 0.001, respectively). A significant reduction of symptomatic drug consumption at 3 and 6 months was reported in the pCGS Group (p < 0.001). No serious adverse event was recorded in both groups. CONCLUSIONS: Despite all the limitations inherent to an observational study, our results suggest the potential effectiveness of pCGS, when used in combination with conventional therapy in EHOA. Further randomized placebo-controlled trials are needed to confirm these positive findings. TRIAL REGISTRATION: ClinicalTrials.gov, http://www. CLINICALTRIALS: gov , date of registration: February 2, 2022, NCT05237596. The present trial was retrospectively registered.

Synovial Fluid Regulates the Gene Expression of a Pattern of microRNA via the NF-κB Pathway: An In Vitro Study on Human Osteoarthritic Chondrocytes.

Synovial fluid (SF) represents the primary source of nutrients of articular cartilage and is implicated in maintaining cartilage metabolism. We investigated the effects of SF, from patients with osteoarthritis (OA), rheumatoid arthritis (RA), and controls, on a pattern of microRNA (miRNA) in human OA chondrocytes. Cells were stimulated with 50% or 100% SF for 24 h and 48 h. Apoptosis and superoxide anion production were detected by cytometry; miRNA (34a, 146a, 155, 181a), cytokines, metalloproteinases (MMPs), type II collagen (Col2a1), antioxidant enzymes, B-cell lymphoma (BCL)2, and nuclear factor (NF)-κB by real-time PCR. The implication of the NF-κB pathway was assessed by the use of NF-κB inhibitor (BAY-11-7082). RA and OA SF up-regulated miR-34a, -146a, -155, -181a, interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, MMP-1, MMP-13, and ADAMTs-5 gene expression, while it down-regulated Col2a1. Pathological SF also induced apoptosis, reduced viability, and decreased BCL2 mRNA, whereas it increased superoxide anions, the expression of antioxidant enzymes, p65 and p50 NF-κB. Opposite and positive results were obtained with 100% control SF. Pre-incubation with BAY-11-7082 counteracted SF effects on miRNA. We highlight the role of the SF microenvironment in regulating some miRNA involved in inflammation and cartilage degradation during OA and RA, via the NF-κB pathway.

Exploring the Crosstalk between Hydrostatic Pressure and Adipokines: An In Vitro Study on Human Osteoarthritic Chondrocytes.

Obesity is a risk factor for osteoarthritis (OA) development and progression due to an altered biomechanical stress on cartilage and an increased release of inflammatory adipokines from adipose tissue. Evidence suggests an interplay between loading and adipokines in chondrocytes metabolism modulation. We investigated the role of loading, as hydrostatic pressure (HP), in regulating visfatin-induced effects in human OA chondrocytes. Chondrocytes were stimulated with visfatin (24 h) and exposed to high continuous HP (24 MPa, 3 h) in the presence of visfatin inhibitor (FK866, 4 h pre-incubation). Apoptosis and oxidative stress were detected by cytometry, B-cell lymphoma (BCL)2, metalloproteinases (MMPs), type II collagen (Col2a1), antioxidant enzymes, miRNA, cyclin D1 expressions by real-time PCR, and ß-catenin protein by western blot. HP exposure or visfatin stimulus significantly induced apoptosis, superoxide anion production, and MMP-3, -13, antioxidant enzymes, and miRNA gene expression, while reducing Col2a1 and BCL2 mRNA. Both stimuli significantly reduced ß-catenin protein and increased cyclin D1 gene expression. HP exposure exacerbated visfatin-induced effects, which were counteracted by FK866 pre-treatment. Our data underline the complex interplay between loading and visfatin in controlling chondrocytes' metabolism, contributing to explaining the role of obesity in OA etiopathogenesis, and confirming the importance of controlling body weight for disease treatment.

A Combination of Celecoxib and Glucosamine Sulfate Has Anti-Inflammatory and Chondroprotective Effects: Results from an In Vitro Study on Human Osteoarthritic Chondrocytes.

This study investigated the possible anti-inflammatory and chondroprotective effects of a combination of celecoxib and prescription-grade glucosamine sulfate (GS) in human osteoarthritic (OA) chondrocytes and their possible mechanism of action. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination with IL-1ß (10 ng/mL) and a specific nuclear factor (NF)-κB inhibitor (BAY-11-7082, 1 µM). Gene expression and release of some pro-inflammatory mediators, metalloproteinases (MMPs), and type II collagen (Col2a1) were evaluated by qRT-PCR and ELISA; apoptosis and mitochondrial superoxide anion production were assessed by cytometry; B-cell lymphoma (BCL)2, antioxidant enzymes, and p50 and p65 NF-κB subunits were analyzed by qRT-PCR. Celecoxib and GS alone or co-incubated with IL-1ß significantly reduced expression and release of cyclooxygenase (COX)-2, prostaglandin (PG)E2, IL-1ß, IL-6, tumor necrosis factor (TNF)-α, and MMPs, while it increased Col2a1, compared to baseline or IL-1ß. Both drugs reduced apoptosis and superoxide production; reduced the expression of superoxide dismutase, catalase, and nuclear factor erythroid; increased BCL2; and limited p50 and p65. Celecoxib and GS combination demonstrated an increased inhibitory effect on IL-1ß than that observed by each single treatment. Drugs effects were potentiated by pre-incubation with BAY-11-7082. Our results demonstrated the synergistic effect of celecoxib and GS on OA chondrocyte metabolism, apoptosis, and oxidative stress through the modulation of the NF-κB pathway, supporting their combined use for the treatment of OA.

A retrospective observational study of glucosamine sulfate in addition to conventional therapy in hand osteoarthritis patients compared to conventional treatment alone.

BACKGROUND: The optimal management of hand osteoarthritis (HOA) is still challenging. AIM: To evaluate the effects of glucosamine sulfate (GS) in addition to conventional therapy compared to conventional therapy alone in HOA. METHODS: This 6-month retrospective study included 108 patients with concomitant knee and hand OA. Fifty-five patients (GS Group) were treated for six consecutive months with crystalline GS (1500 mg once/day) in addition to conventional therapy for HOA [exercise combined with acetaminophen and/or non-steroidal anti-inflammatory drugs (NSAIDs)] and 53 patients (Control Group) with the conventional therapy alone. Primary outcomes were the difference between groups in the change of hand pain on a Visual Analogue Scale (VAS) and in the Functional Index for Hand Osteoarthritis (FIHOA) from baseline to 6 months. Secondary outcomes were Health Assessment Questionnaire (HAQ), medical outcomes study 36-item short form (SF-36) and symptomatic drug consumption. RESULTS: The patients who received GS presented a significant decrease (p < 0.001) in VAS pain and FIHOA scores compared with the Control Group at 3 and 6 months. Furthermore, GS therapy was associated to a significant improvement of HAQ score and to a significant reduction of acetaminophen and NSAID consumption during the follow-up. No differences in the number of side effects were observed between the groups. DISCUSSION: GS could represent a potential successful therapy for HOA and should be tried in large randomized placebo and active controlled trials. CONCLUSIONS: The combination of GS with conventional treatment seems to be more effective in improving pain and function than conventional HOA treatment alone. TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.gov date of registration: April 9, 2019, NCT03911570. The present trial was retrospectively registered.

A comprehensive analysis to understand the mechanism of action of balneotherapy: why, how, and where they can be used? Evidence from in vitro studies performed on human and animal samples.

Balneotherapy (BT) is one of the most commonly used complementary therapies for many pathological conditions. Its beneficial effects are related to physical and chemical factors, but the exact mechanism of action is not fully understood. Recently, there has been an increased interest in the use of preclinical models to investigate the influence of BT on inflammation, immunity, and cartilage and bone metabolism. The objective of this comprehensive analysis was to summarize the current knowledge about the in vitro studies in BT and to revise the obtained results on the biological effects of mineral waters. Special attention has been paid to the main rheumatological and dermatological conditions, and to the regulation of the immune response. The objective of this review was to summarize the in vitro studies, on human and animal samples, investigating the biological effects of BT. In particular, we analyzed the properties of a thermal water, as a whole, of an inorganic molecule, such as hydrogen sulfide in different cell cultures (keratinocytes, synoviocytes, chondrocytes, and peripheral blood cells), or of the organic component. The results corroborated the scientific value of in vitro studies in demonstrating the anti-inflammatory, antioxidant, chondroprotective, and immunosuppressive role of BT at the cellular level. However, the validity of the cell culture model is limited by several sources of bias, as the differences in experimental procedures, the high heterogeneity among the available researches, and the difficulties in considering all the chemical and physical factors of BT. We would like to stimulate the scientific community to standardize the experimental procedures and enhance in vitro research in the field of BT.

Sulfurous-arsenical-ferruginous balneotherapy for osteoarthritis of the hand: results from a retrospective observational study.

Balneotherapy (BT) is a complementary therapy widely used in several rheumatic conditions, however, the evidence in hand osteoarthritis (HOA) is still scarce. The aim of this preliminary study is to retrospectively evaluate the symptomatic effects of a cycle of mud-bath therapy in HOA patients. Two hundred twelve outpatients with primary bilateral HOA treated with 12 daily local mud packs and generalized thermal baths with a sulfurous-arsenical-ferruginous mineral water added to usual treatment were included in the study. Each patient was examined at baseline and at the end of thermal therapy (2 weeks). Primary outcome measures were global spontaneous hand pain on a Visual Analogue Scale (VAS) and the Functional Index for Hand Osteoarthritis (FIHOA) score; secondary outcomes were handgrip strength, duration of morning stiffness, Health Assessment Questionnaire (HAQ), Short Form Health Survey (SF-12), tolerability and patients' and physicians' global impression of treatment efficacy and tolerability. Our results demonstrated that the efficacy of mud-bath therapy was significant in all the assessed parameters at the end of therapy, except for the physical component score of SF-12. The thermal treatment was well tolerated. The patient's and the physician's global assessments showed a high level of satisfaction in terms of efficacy and safety. In conclusion, our results may suggest a short-term effectiveness of mud-bath therapy in controlling pain and improving functionality in HOA patients, supporting the role of this treatment as a complementary strategy in the management of HOA; however, further randomized controlled trials with a long-term follow-up are needed.

Aromatase Inhibitors-Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects.

Aromatase inhibitors (AIs) have radically changed the prognosis of hormone receptor positive breast cancer (BC) in post-menopausal women, and are a mainstay of the adjuvant therapy for BC after surgery in place of, or following, Tamoxifen. However, AIs aren't side effect-free; frequent adverse events involve the musculoskeletal system, in the form of bone loss, AI-associated arthralgia (AIA) syndrome and autoimmune rheumatic diseases. In this narrative review, we reported the main clinical features of these three detrimental conditions, their influence on therapy adherence, the possible underlying molecular mechanisms and the available pharmacological and non-pharmacological treatments. The best-known form is the AIs-induced osteoporosis, whose molecular pathway and therapeutic possibilities were extensively investigated in the last decade. AIA syndrome is a high prevalent joint pain disorder which often determines a premature discontinuation of the therapy. Several points still need to be clarified, as a universally accepted diagnostic definition, the pathogenetic mechanisms and satisfactory management strategies. The association of AIs therapy with autoimmune diseases is of the utmost interest. The related literature has been recently expanded, but many issues remain to be explored, the first being the molecular mechanisms.

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes.

Hydrostatic pressure (HP) modulates chondrocytes metabolism, however, its ability to regulate oxidative stress and microRNAs (miRNA) has not been clarified. The aim of this study was to investigate the role of miR-34a, miR-146a, and miR-181a as possible mediators of HP effects on oxidative stress in human osteoarthritis (OA) chondrocytes. Chondrocytes were exposed to cyclic low HP (1-5 MPa) and continuous static HP (10 MPa) for 3 hrs. Metalloproteinases (MMPs), disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5, type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma 2 (BCL2) were evaluated by quantitative real-time polymerase chain reaction qRT-PCR, apoptosis and reactive oxygen species ROS production by cytometry, and ß-catenin by immunofluorescence. The relationship among HP, the studied miRNA, and oxidative stress was assessed by transfection with miRNA specific inhibitors. Low cyclical HP significantly reduced apoptosis, the gene expression of MMP-13, ADAMTS5, miRNA, the production of superoxide anion, and mRNA levels of antioxidant enzymes. Conversely, an increased Col2a1 and BCL2 genes was observed. ß-catenin protein expression was reduced in cells exposed to HP 1-5 MPa. Opposite results were obtained following continuous static HP application. Finally, miRNA silencing enhanced low HP and suppressed continuous HP-induced effects. Our data suggest miRNA as one of the mechanisms by which HP regulates chondrocyte metabolism and oxidative stress, via Wnt/ß-catenin pathway.

Tocilizumab modulates serum levels of adiponectin and chemerin in patients with rheumatoid arthritis: potential cardiovascular protective role of IL-6 inhibition.

OBJECTIVES: Adipokines play an important role in the pathophysiology of rheumatoid arthritis (RA), provide a link between the disease and overweight, contributing to explain the enhanced cardiovascular (CV) risk and influence the response to disease-modifying anti-rheumatic drugs. The aim of this study was to determine the possible effects of intravenous (IV) tocilizumab (TCZ), an interleukin-6 receptor antagonist, on serum levels of leptin, adiponectin, resistin, visfatin, and chemerin. METHODS: Forty-four RA patients with active disease (DAS28-ESR ≥3.2) were treated with IV TCZ (8 mg/kg) once every 4 weeks for six months: 20 patients received TCZ as monotherapy and 24 in association with methotrexate (MTX). At baseline and monthly, before each infusion, body mass index, DAS28-ESR and Health Assessment Questionnaire (HAQ) were recorded. The laboratory parameters, including the adipokines serum levels were collected at baseline and after six months. RESULTS: At the end of the follow-up, ESR, CRP, DAS28-ESR and HAQ resulted significantly improved in patients received TCZ as monotherapy or combined with MTX. Lipid profile showed only a significant increase of total cholesterol. A significant reduction of chemerin and an increase of adiponectin were observed in the whole population and in the subgroups of the patients analysed (TCZ mono or combined therapy) without any significant correlations with clinical and biochemical parameters. No changes in the leptin and resistin levels were detected. CONCLUSIONS: TCZ is able to regulate serum levels of chemerin and adiponectin in RA patients, independently of the disease treatment response, which contributes to explain the CV safety of TCZ.

Sarcopenia in systemic sclerosis: the impact of nutritional, clinical, and laboratory features.

We evaluated the presence of sarcopenia in a population of systemic sclerosis (SSc) patients, with respect to nutritional, clinical, and laboratory features. A total of 62 patients who met the ACR/EULAR 2013 classification criteria were enrolled. Sarcopenia was defined according to the Relative Skeletal Mass Index (RSMI) and hand grip strength (HGS). Body composition was assessed with the calculation of the Body Mass Index (BMI), lean body mass (LBM) and fat mass (FM). Malnutrition was evaluated according to the ESPEN criteria. Clinical evaluation included nailfold capillaroscopy and skin evaluation by modified Rodnan Skin Score (mRSS), pulmonary function tests (PFT) with diffusing capacity for carbon monoxide adjusted for hemoglobin (DLCO), high-resolution computed tomography (HR-CT) of the lungs, echocardiography and high-resolution manometry (HRM) for esophageal involvement. Laboratory evaluation included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, creatinine, creatine kinase (CK), transaminases, lipid profile, glycemia, albumin, and vitamin-D. Antinuclear antibodies (ANA) and extractable nuclear antigens (ENA) were also assessed. Considering RSMI, the prevalence of sarcopenia is 42%. In this case, age, malnutrition, disease duration, mRSS, capillaroscopy score, esophageal involvement, ESR, and ANA titer are higher in the sarcopenic group, while DLCO and LBM are lower. Considering HGS, the prevalence of sarcopenia is 55%. Age, disease duration, malnutrition, FM, mRSS, capillaroscopy score, esophageal involvement, ESR, and ENA positivity are higher in the sarcopenic group, while DLCO is lower. By using both RSMI and HGS to assess sarcopenia in SSc, the results of this study demonstrated that this condition correlates with different nutritional, clinical, and biochemical parameters associated with the worsening of the disease.

Exploring the Involvement of NLRP3 and IL-1ß in Osteoarthritis of the Hand: Results from a Pilot Study.

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1ß plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The aim of this study was to investigate the involvement of IL-1ß and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in patients with EHOA and nonerosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1ß and NLRP3, the serum levels of IL-1ß, IL-6, IL-17, and tumor necrosis factor- (TNF-) α, and the protein levels of IL-1ß and NLRP3. We also assessed the relationships between IL-1ß and NLRP3 and clinical, laboratory, and radiological findings. Fifty-four patients with HOA (25 EHOA and 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cell (PBMC) gene and protein expressions of IL-1ß and NLRP3 were quantified by quantitative real-time PCR and western blot. IL-1ß, IL-6, IL-17, and TNF-α serum levels were determined by ELISA. IL-1ß gene expression was significantly reduced (p = 0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in the NEHOA group versus the control (p = 0.0063) and EHOA groups (p = 0.0038). IL-1ß serum levels were not significantly different across the groups; IL-6, IL-17, and TNF-α were not detectable in any sample. IL-1ß concentrations were negatively correlated with the Kellgren-Lawrence score in the whole population (r = -0.446; p = 0.0008) and in NEHOA (r = -0.608; p = 0.004), while IL-1ß gene expression was positively correlated with the number of joint swellings in the EHOA group (r = 0.512; p = 0.011). Taken together, our results, showing poorly detectable IL-1ß concentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at the local level.

MicroRNA Mediate Visfatin and Resistin Induction of Oxidative Stress in Human Osteoarthritic Synovial Fibroblasts Via NF-κB Pathway.

Synovial membrane inflammation actively participate to structural damage during osteoarthritis (OA). Adipokines, miRNA, and oxidative stress contribute to synovitis and cartilage destruction in OA. We investigated the relationship between visfatin, resistin and miRNA in oxidative stress regulation, in human OA synovial fibroblasts. Cultured cells were treated with visfatin and resistin. After 24 h, we evaluated various pro-inflammatory cytokines, metalloproteinases (MMPs), type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma (BCL)2 by qRT-PCR, apoptosis and mitochondrial superoxide production by cytometry, p50 nuclear factor (NF)-κB by immunofluorescence. Synoviocytes were transfected with miRNA inhibitors and oxidative stress evaluation after adipokines stimulus was performed. The implication of NF-κB pathway was assessed by the use of a NF-κB inhibitor (BAY-11-7082). Visfatin and resistin significantly up-regulated gene expression of interleukin (IL)-1ß, IL-6, IL-17, tumor necrosis factor (TNF)-α, MMP-1, MMP-13 and reduced Col2a1. Furthermore, adipokines induced apoptosis and superoxide production, the transcriptional levels of BCL2, superoxide dismutase (SOD)-2, catalase (CAT), nuclear factor erythroid 2 like 2 (NRF2), miR-34a, miR-146a, and miR-181a. MiRNA inhibitors counteracted adipokines modulation of oxidative stress. Visfatin and resistin effects were suppressed by BAY-11-7082. Our data suggest that miRNA may represent possible mediators of oxidative stress induced by visfatin and resistin via NF-κB pathway in human OA synoviocytes.

A Complex Relationship between Visfatin and Resistin and microRNA: An In Vitro Study on Human Chondrocyte Cultures.

Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthritis (OA) pathogenesis. The purpose of the present study was to investigate the effect of visfatin and resistin on some miRNA (34a, 140, 146a, 155, 181a, let-7e), metalloproteinases (MMPs), and collagen type II alpha 1 chain (Col2a1) in human OA chondrocytes and in the T/C-28a2 cell line. The implication of nuclear factor (NF)-κB in response to adipokines was also assessed. Chondrocytes were stimulated with visfatin (5 or 10 µg/mL) and resistin (50 or 100 ng/mL) with or without NF-κB inhibitor (BAY-11-7082, 1 µM) for 24 h. Viability and apoptosis were detected by MMT and cytometry, miRNA, MMP-1, MMP-13, and Col2a1 by qRT-PCR and NF-κB activation by immunofluorescence. Visfatin and resistin significantly reduced viability, induced apoptosis, increased miR-34a, miR-155, miR-181a, and miR-let7e, and reduced miR-140 and miR-146a gene expression in OA chondrocytes. MMP-1, MMP-13, and Col2a1 were significantly modulated by treatment of OA chondrocytes with adipokines. Visfatin and resistin significantly increased NF-κB activation, while the co-treatment with BAY11-7082 did not change MMPs or Col2a1 levels beyond that caused by single treatment. Visfatin and resistin regulate the expression levels of some miRNA involved in OA pathogenesis and exert catabolic functions in chondrocytes via the NF-κB pathway. These data confirm the complex relationship between adipokines and miRNA.

Do MicroRNAs have a key epigenetic role in osteoarthritis and in mechanotransduction?

Osteoarthritis (OA) is the most common degenerative disease affecting joint tissues. The pathogenesis of OA is complex and poorly understood, as well as the multiple factors contributing to its development and progression. Accumulating evidence has suggested that microRNAs (miRNAs) play an important role as regulators of cartilage biology and in the pathogenesis of OA. It has been demonstrated that mechanical loading, important for the regulation of cartilage metabolism, affects miRNAs expression. Furthermore, miRNAs present in human plasma and in synovial fluid could represent promising biological markers for OA. Herein, we have reviewed the current state of research on miRNAs in cartilage homeostasis and OA pathogenesis and their potential clinical applications.

Can hybrid hyaluronic acid represent a valid approach to treat rizoarthrosis? A retrospective comparative study.

BACKGROUND: Osteoarthritis (OA) of the trapeziometacarpal joint (TMJ) is a disabling condition with a significant impact on quality of life. The optimal management of hand OA requires a combination of non-pharmacological and pharmacological treatments that include intra-articular (i.a.) therapy. EULAR experts recommend corticosteroid injections in TMJ OA and underline the usefulness of hyaluronic acid (HA). The aim of this study was the assessment of the efficacy and tolerability of i.a. injections of a hybrid formulation of HA (Sinovial H-L®) in comparison to triamcinolone in patients with TMJ OA. METHODS: This 6-months observational comparative study, retrospective analyzed the medical records of 100 patients with monolateral or bilateral TMJ OA, treated with two injections of Sinovial H-L® (Sinovial H-L Group) or of triamcinolone acetonide (Triamcinolone Group). Clinical assessments were recorded at the time of the first and second injection and after one, 3 and 6 months. The primary outcomes were the change in global pain on a Visual Analogue Scale (VAS) and in hand function evaluated by the Functional Index for Hand OA (FIHOA) from baseline to month 6. Secondary outcomes were the improvement of the duration of morning stiffness, Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study 36-Item Short Form (SF-36). The comparison between the two groups of treatment were performed with the Wilcoxon rank-sum test for continuous variables and with chi-square or Fisher exact test for categorical variables. Statistical significance was set at p < 0.05. RESULTS: Both therapies provided effective pain relief and joint function improvement, but the benefits achieved were statistically significantly superior in the Sinovial H-L Group than the Triamcinolone Group after one month (p < 0.01) from the beginning of the therapy and during the 6-months follow-up (p < 0.001). Furthermore, Sinovial H-L® was associated with a significant decrease in the duration of morning stiffness and with a significant improvement in the HAQ score and physical component summary (PCS)-SF-36. CONCLUSIONS: Our results suggested that the hybrid formulation of HA may be more effective than triamcinolone in pain relief and joint function improvement with a rapid and persistent effect, resulting a valid alternative to steroid in the management of TMJ OA. TRIAL REGISTRATION: ClinicalTrials.gov, date of registration: June 14, 2017, NCT03200886 . The present trial was retrospectively registered.

Could Oxidative Stress Regulate the Expression of MicroRNA-146a and MicroRNA-34a in Human Osteoarthritic Chondrocyte Cultures?

Oxidative stress and the overproduction of reactive oxygen species (ROS) play an important role in the pathogenesis of osteoarthritis (OA). Accumulating evidence has demonstrated the involvement of microRNAs (miRNAs) dysregulation in disease development and progression. In this study, we evaluated the effect of oxidative stress on miR-146a and miR-34a expression levels in human OA chondrocytes cultures stimulated by H2O2. Mitochondrial ROS production and cell apoptosis were detected by flow cytometry. The antioxidant enzymes SOD-2, CAT, GPx, the transcriptional factor NRF2 and the selected miRNAs were analyzed by qRT-PCR. The H2O2-induced oxidative stress was confirmed by a significant increase in superoxide anion production and of the apoptotic ratio. Furthermore, H2O2 significantly up-regulated the expression levels of SOD-2, CAT, GPx and NRF2, and modulated miR-146a and miR-34a gene expression. The same analyses were carried out after pre-treatment with taurine, a known antioxidant substance, which, in our experience, counteracted the H2O2-induced effect. In conclusion, the induction of oxidative stress affected cell apoptosis and the expression of the enzymes involved in the oxidant/antioxidant balance. Moreover, we demonstrated for the first time the modification of miR-146a and miR-34a in OA chondrocytes subjected to H2O2 stimulus and we confirmed the antioxidant effect of taurine.

One year in review 2016: idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are a group of rare, acquired, clinically heterogeneous autoimmune inflammatory muscle disorders characterised by muscle weakness and multisystem involvement. Recently, new concepts about pathogenesis, diagnosis and treatment of these complex diseases have been provided. The purpose of this manuscript is to summarise the most relevant literature contributions published over the last year.

May spa therapy be a valid opportunity to treat hand osteoarthritis? A review of clinical trials and mechanisms of action.

Osteoarthritis (OA) is the most common form of arthritis and its current treatment includes non-pharmacological and pharmacological modalities. Spa therapy represents a popular treatment for many rheumatic diseases. The aim of this review was to summarize the currently available information on clinical effects and mechanisms of action of spa therapy in OA of the hand. We conducted a search of the literature to extract articles describing randomized clinical trials (RCTs) in hand OA published in the period 1952-2015. We identified three assessable articles reporting RCTs on spa therapy in hand OA. Data from these clinical trials support a beneficial effect of spa therapy on pain, function and quality of life in hand OA. Spa therapy seems to have a role in the treatment of hand OA. However, additional RCTs are necessary to clarify the mechanisms of action and the effects of the application of thermal treatments.

Spa therapy: can be a valid option for treating knee osteoarthritis?

Osteoarthritis (OA) continues to be one of the leading causes of 'years lived with disability' worldwide. Symptomatic knee OA is highly prevalent among people aged 50 years and over and is destined to become an ever more important healthcare problem. Current management of knee OA includes non-pharmacological and pharmacological treatments. Spa therapy is one of the most commonly used non-pharmacological approaches for OA in many European countries, as well as in Japan and Israel. Despite its long history and popularity, spa treatment is still the subject of debate and its role in modern medicine continues to be unclear. The objective of this review is to summarize the currently available information on clinical effects and mechanisms of action of spa therapy in knee OA. Various randomized controlled clinical trials (RCTs) were conducted to assess the efficacy and tolerability of balneotherapy and mud-pack therapy in patients with knee OA. Data from these clinical trials support a beneficial effect of spa therapy on pain, function and quality of life in knee OA that lasts over time, until 6-9 months after the treatment. The mechanisms by which immersion in mineral or thermal water or the application of mud alleviate suffering in OA are not fully understood. The net benefit is probably the result of a combination of factors, among which the mechanical, thermal and chemical effects are most prominent. In conclusion, spa therapy seems to have a role in the treatment of knee OA. Additional RCTs and further studies of mechanisms of action with high methodological quality are necessary to prove the effects of spa therapy.