REG-O3 chimeric peptide combining growth hormone and somatostatin sequences improves joint function and prevents cartilage degradation in rat model of traumatic knee osteoarthritis.

Objective: REG-O3 is a 24-aminoacid chimeric peptide combining a sequence derived from growth hormone (GH) and an analog of somatostatin (SST), molecules displaying cartilage repair and anti-inflammatory properties, respectively. This study aimed to investigate the disease-modifying osteoarthritis drug (DMOAD) potential of REG-O3 by analyzing its effect on pain, joint function and structure, upon injection into osteoarthritic rat knee joint.

Design: Osteoarthritis was induced in the right knee of mature male Lewis rats (n = 12/group) by surgical transection of the anterior cruciate ligament (ACLT) combined with partial medial meniscectomy (pMMx).

From Translation to Protein Degradation as Mechanisms for Regulating Biological Functions: A Review on the SLRP Family in Skeletal Tissues.

The extracellular matrix can trigger cellular responses through its composition and structure. Major extracellular matrix components are the proteoglycans, which are composed of a core protein associated with glycosaminoglycans, among which the small leucine-rich proteoglycans (SLRPs) are the largest family. This review highlights how the codon usage pattern can be used to modulate cellular response and discusses the biological impact of post-translational events on SLRPs, including the substitution of glycosaminoglycan moieties, glycosylation, and degradation.

The secretome of skeletal muscle cells: A systematic review.

Background: Proteomic studies of the secretome of skeletal muscle cells can help us understand the processes that govern the synthesis, systemic interactions and organization of skeletal muscle and identify proteins that are involved in muscular adaptations to exercise, ageing and degeneration. In this systematic review, we aimed to summarize recent mass-spectrometry based proteomics discoveries on the secretome of skeletal muscle cells in response to disease, exercise or metabolic stress.

Methods: A literature search was performed in the Medline/Ovid and Scopus electronic bibliographic databases.

Healing of Diabetic Neuroischemic Foot Wounds With vs Without Wound-Targeted Revascularization: Preliminary Observations From an 8-Year Prospective Dual-Center Registry.

To assess the clinical efficacy of endovascular angiosome-oriented wound-targeted revascularization (WTR) vs indirect (wound-indifferent) revascularization (IR) in diabetic patients with neuroischemic foot ulcers. Between April 2009 and July 2017, 167 diabetic patients (mean age 72.8 years; 137 men) with chronic limb-threatening ischemia (Rutherford category 5) and foot wounds (Wagner 2-4) in 194 limbs were prospectively registered and scheduled for primary infragenicular endovascular treatment.

Type II collagen peptide Coll2-1 is an actor of synovitis.

Objective: We evaluated the ability of Coll2-1, a type II collagen peptide, to activate pro-inflammatory pathways in synovial cells and to induce arthritis in Lewis rats.

Method: Human synoviocytes and chondrocytes from knee OA patients were cultured for 24 h with/without Coll2-1 and/or purified immunoglobulin G (AS0619) binding specifically this peptide, and/or CLI-095, a TLR-4 signaling inhibitor and/or apocynin and diphenyleneiodonium, Reactive oxygen species (ROS) production inhibitors. The Interleukin (IL)-8 and Vascular Endothelium Growth Factor (VEGF) expression, the IL-8 production, the IκB-α and p65 phosphorylation and ROS were evaluated.

Protective Actions of Oral Administration of CBi0703 in Spontaneous Osteoarthritis in Dunkin Hartley Guinea Pig Model.

Objective: The aim of this study was to evaluate the effects of a lyophilized inactivated culture (LIC) from CBi0703 in a spontaneous model of osteoarthritis (OA) in Dunkin Hartley guinea pigs. Histology of cartilage and synovial membrane was the primary outcome. Biomarkers were also considered to evaluate the treatment efficacy.

Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: biochemical markers associated with emerging clinical phenotypes and molecular endotypes.

Purpose Of Review: This review focuses on the molecular taxonomy of osteoarthritis from the perspective of molecular biomarkers. We discuss how wet biochemical markers may be used to understand disease pathogenesis and progression and define molecular endotypes of osteoarthritis and how these correspond to clinical phenotypes.

Recent Findings: Emerging evidence suggests that osteoarthritis is a heterogeneous and multifaceted disease with multiple causes, molecular endotypes and corresponding clinical phenotypes.

Natural Products for Promoting Joint Health and Managing Osteoarthritis.

Purpose Of Review: Osteoarthritis, the most common joint disease, is associated with substantial medical costs, lost productivity, and reduced quality of life. However, available pharmaceutical treatments have limitations in terms of efficacy and long-term safety.

Recent Findings: In vitro evidence suggests that some natural products may possess anti-inflammatory and anti-oxidative properties and may inhibit the release of key osteoarthritis-related cytokines.

Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo.

Background: Changes of serum concentrations of glycated, oxidized, and nitrated amino acids and hydroxyproline and anticyclic citrullinated peptide antibody status combined by machine learning techniques in algorithms have recently been found to provide improved diagnosis and typing of early-stage arthritis of the knee, including osteoarthritis (OA), in patients. The association of glycated, oxidized, and nitrated amino acids released from the joint with development and progression of knee OA is unknown. We studied this in an OA animal model as well as interleukin-1β-activated human chondrocytes in vitro and translated key findings to patients with OA.

A randomized, double-blind, prospective, placebo-controlled study of the efficacy of a diet supplemented with curcuminoids extract, hydrolyzed collagen and green tea extract in owner's dogs with osteoarthritis.

Background: We have previously demonstrated that a mixture of Curcuminoids extract, hydrolyzed COllagen and green Tea extract (CCOT) inhibited inflammatory and catabolic mediator's synthesis by bovine and human chondrocytes. A randomly allocated, double-blind, prospective, placebo-controlled study was performed to evaluate the efficacy of a diet containing this CCOT mixture on dogs with naturally occurring osteoarthritis (OA). Therefore, 42 owner's dogs with OA were randomly assigned to receive for 3 months an experimental diet (control) or the same diet supplemented with CCOT.

Soluble biochemical markers of osteoarthritis: Are we close to using them in clinical practice?

Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability. Recent work suggests that the global burden of OA is increasing, and costs associated with treatment are expected to increase dramatically as the aging human population expands. OA is currently diagnosed using radiography, but this technique is an indirect and insensitive measure of alterations in articular cartilage and fails to measure dynamic inflammatory processes in the joint.

Midterm Outcomes From a Pilot Study of Percutaneous Deep Vein Arterialization for the Treatment of No-Option Critical Limb Ischemia.

Purpose: To report the initial clinical experience with percutaneous deep vein arterialization (PDVA) to treat critical limb ischemia (CLI) via the creation of an arteriovenous fistula.

Methods: Seven patients (median age 85 years; 5 women) with CLI and no traditional endovascular or surgical revascularization options (no-option CLI) were recruited in a pilot study to determine the safety of PDVA. All patients were diabetic; 4 had Rutherford category 6 ischemia.

Relationship between weight loss in obese knee osteoarthritis patients and serum biomarkers of cartilage breakdown: secondary analyses of a randomised trial.

Objective: To explore effects of weight loss and maintenance on serum cartilage biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment (Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic improvement, in a knee osteoarthritis (KOA) population.

Design: 192 obese KOA patients followed a 16 week weight loss intervention and 52 weeks weight maintenance (ClinicalTrials.gov identifier: NCT00655941).

Review of Soluble Biomarkers of Osteoarthritis: Lessons From Animal Models.

Objective Osteoarthritis (OA) is one of the leading causes of disability within the adult population. Currently, its diagnosis is mainly based on clinical examination and standard radiography. To date, there is no way to detect the disease at a molecular level, before the appearance of structural changes and symptoms.

Altered Expression of MicroRNAs in Rheumatoid Arthritis.

Rheumatoid arthritis is one of the most common types of inflammatory joint diseases. Women, smokers, and people with positive family history are more susceptible to this disease. Diagnostic criteria include at least one swollen joint that has not been caused by other diseases.

Chitosan: A promising polymer for cartilage repair and viscosupplementation.

Osteoarthritis (OA) is a painful, degenerative and inflammatory disease that affects the entire synovial joints. Nowadays, no cure exists, and the pharmacological treatments are limited to symptoms alleviation. There is a need for a new efficient and safe treatment.

Identification of Targets of a New Nutritional Mixture for Osteoarthritis Management Composed by Curcuminoids Extract, Hydrolyzed Collagen and Green Tea Extract.

Objective: We have previously demonstrated that a mixture of curcuminoids extract, hydrolyzed collagen and green tea extract (COT) inhibited inflammatory and catabolic mediator's synthesis by osteoarthritic human chondrocytes. The objective of this study was to identify new targets of COT using genomic and proteomic approaches.

Design: Cartilage specimens were obtained from 12 patients with knee osteoarthritis.

Osteoarthritis biomarkers derived from cartilage extracellular matrix: Current status and future perspectives.

Specific soluble biomarkers can be powerful tools for the diagnosis, prognosis and personalized management of osteoarthritis (OA). Biomarkers are potential indicators of the effect of a drug on cartilage metabolism and provide crucial information about the mechanisms of drug action. In this review, we address key questions concerning the use of biomarkers in OA management: Why do we need soluble biomarkers? What are the most widely investigated biomarkers derived from cartilage extracellular matrix? What are the most common pitfalls in interpreting soluble biomarker measurements? What are the perspectives and future research directions in this field? We review current evidence to propose that cartilage-derived soluble biomarkers are complementary "drug development tools" that can be applied during drug development from preclinical research to clinical evaluation.

Soluble biomarkers development in osteoarthritis: from discovery to personalized medicine.

Context: Specific soluble biomarkers could be a precious tool for diagnosis, prognosis and personalized management of osteoarthritic (OA) patients.

Objective: To describe the path of soluble biomarker development from discovery to clinical qualification and regulatory adoption toward OA-related biomarker qualification.

Methods And Results: This review summarizes current guidance on the use of biomarkers in OA in clinical trials and their utility at five stages, including preclinical development and phase 1 to phase 4 trials.

Biomarkers of (osteo)arthritis.

Arthritic diseases are a major cause of disability and morbidity, and cause an enormous burden for health and social care systems globally. Osteoarthritis (OA) is the most common form of arthritis. The key risk factors for the development of OA are age, obesity, joint trauma or instability.

Analgesic Efficacy and Safety of Curcuminoids in Clinical Practice: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Curcuminoids are natural products with potent anti-inflammatory and antioxidant properties. There have been a number of reports on the analgesic effects of curcuminoids in clinical trials, yet data have not been fully conclusive.

Objectives: To provide the highest level of evidence on the efficacy of curcuminoids in patients with painful conditions through meta-analysis of data from randomized controlled trials (RCTs).

Carnosol Inhibits Pro-Inflammatory and Catabolic Mediators of Cartilage Breakdown in Human Osteoarthritic Chondrocytes and Mediates Cross-Talk between Subchondral Bone Osteoblasts and Chondrocytes.

Aim: The aim of this work was to evaluate the effects of carnosol, a rosemary polyphenol, on pro-inflammatory and catabolic mediators of cartilage breakdown in chondrocytes and via bone-cartilage crosstalk.

Materials And Methods: Osteoarthritic (OA) human chondrocytes were cultured in alginate beads for 4 days in presence or absence of carnosol (6 nM to 9 μM). The production of aggrecan, matrix metalloproteinase (MMP)-3, tissue inhibitor of metalloproteinase (TIMP)-1, interleukin (IL)-6 and nitric oxide (NO) and the expression of type II collagen and ADAMTS-4 and -5 were analyzed.