Osteomodulin downregulation is associated with osteoarthritis development.

Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA), and osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA.

Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: A scoping review.

Objective: Osteoarthritis (OA) is the most common degenerative joint disease, characterized by a progressive loss of cartilage associated with synovitis and subchondral bone remodeling. There is however no treatment to cure or delay the progression of OA. The objective of this manuscript was to provide a scoping review of the preclinical and clinical studies reporting the effect of gene therapies for OA.

and Extracts Modulate Different and Complementary Pathways on Human Chondrocytes : Deciphering of a Transcriptomic Study.

(CL) and (BS) extracts are used to relieve osteoarthritis symptoms. The aim of this study was to investigate their mechanisms of action at therapeutic plasmatic concentrations on primary human osteoarthritic (OA) chondrocytes. BS (10-50 μg/ml) and CL (0.

Composition Analysis and Pharmacological Activity of Avocado/Soybean Unsaponifiable Products Used in the Treatment of Osteoarthritis.

Avocado/soybean unsaponifiables (ASUs) are commonly used to treat OA symptoms. However, there are many ASU mixtures on the market with differing compositions and pharmacological activities. This study aimed to compare the composition and pharmacological activity of seven commercially available ASU products on human osteoarthritis chondrocytes.

The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature.

During the osteoarthritis (OA) process, activation of immune systems, whether innate or adaptive, is strongly associated with low-grade systemic inflammation. This process is initiated and driven in the synovial membrane, especially by synovium cells, themselves previously activated by damage-associated molecular patterns (DAMPs) released during cartilage degradation. These fragments exert their biological activities through pattern recognition receptors (PRRs) that, as a consequence, induce the activation of signaling pathways and beyond the release of inflammatory mediators, the latter contributing to the vicious cycle between cartilage and synovial membrane.

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.

Syndecan-4 Is Increased in Osteoarthritic Knee, but Not Hip or Shoulder, Articular Hypertrophic Chondrocytes.

Objective: Syndecan-4 plays a critical role in cartilage degradation during osteoarthritis (OA). The aim of this study was to investigate the expression and localization of syndecan-4 in different OA joint tissues.

Design: Syndecan-4 mRNA levels were quantified by reverse transcription-polymerase chain reaction in human OA primary cells.

Coll2-1 and Coll2-1NO2 as exemplars of collagen extracellular matrix turnover - biomarkers to facilitate the treatment of osteoarthritis?

: Osteoarthritis (OA) is the most common form of arthritis. However, there are no structure or disease-modifying OA drugs (DMOADs). Introducing personalized healthcare to patients and health-care practitioners is a high priority for the management of arthritic and musculoskeletal diseases.

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.

Comparison of secretome from osteoblasts derived from sclerotic versus non-sclerotic subchondral bone in OA: A pilot study.

Objective: Osteoarthritis (OA) is characterized by cartilage degradation but also by other joint tissues modifications like subchondral bone sclerosis. In this study, we used a proteomic approach to compare secretome of osteoblast isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone.

Design: Secretome was analyzed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system.

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.

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.

Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane.

Objective: To compare the gene expression patterns of synovial cells from inflamed or normal/reactive areas of synovial membrane obtained from the same patient with osteoarthritis (OA).

Methods: At the time of total knee replacement, synovial tissues were obtained from 12 patients with knee OA. The inflammation status of the synovial membrane was characterized according to macroscopic criteria and classified as normal/reactive or inflamed.

Targeting the synovial angiogenesis as a novel treatment approach to osteoarthritis.

Synovitis is a key feature in osteoarthritis and is associated with symptom severity. Synovial membrane inflammation is secondary to cartilage degradation which occurs in the early stage and is located adjacent to cartilage damage. This inflammation is characterized by the invasion and activation of macrophages and lymphocytes, the release in the joint cavity of large amounts of pro-inflammatory and procatabolic mediators, and by a local increase of synovial membrane vascularity.

A role for the canonical nuclear factor-κB pathway in coupling neurotrophin-induced differential survival of developing spiral ganglion neurons.

Neurotrophins are key players of neural development by controlling cell death programs. However, the signaling pathways that mediate their selective responses in different populations of neurons remain unclear. In the mammalian cochlea, sensory neurons differentiate perinatally into type I and II populations both expressing TrkB and TrkC, which bind respectively brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3).

Importance of synovitis in osteoarthritis: evidence for the use of glycosaminoglycans against synovial inflammation.

Objectives: After detailing the different aspects of synovial inflammation (i.e., cellular, biochemical, and vascular) and based on the current knowledge, the aim of this review was to collect the available in vitro and in vivo data regarding the potency of some glycosaminoglycan (GAG) compounds to target synovial inflammation, an important aspect of osteoarthritis.

Chondroitin and glucosamine in the management of osteoarthritis: an update.

The objective of osteoarthritis (OA) treatment is not only control of symptoms (i.e. reducing pain and improving function) but also to preserve joint structure and maintain quality of life.

Characterization of synovial angiogenesis in osteoarthritis patients and its modulation by chondroitin sulfate.

Introduction: This work aimed at comparing the production of inflammatory and pro- and anti-angiogenic factors by normal/reactive (N/R) or inflammatory (I) areas of the osteoarthritic synovial membrane. The effects of interleukin (IL)-1β and chondroitin sulfate (CS) on the expression of pro- and anti-angiogenic factors by synovial fibroblasts cells (SFC) were also studied.

Methods: Biopsies from N/R or from I areas of osteoarthritic synovial membrane were collected at the time of surgery.

Chondroitin sulfate in the treatment of osteoarthritis: from in vitro studies to clinical recommendations.

Chondroitin sulfate (CS) is recommended as a therapeutic intervention in the multimodal approach of osteoarthritis (OA) management. CS has been studied extensively to describe its pharmacology (pharmacokinetic, in vitro and in vivo effects) and its clinical efficacy. Various results have been reported depending on the system of evaluation (model, dosage and duration) and the source of CS (origin and quality).

Further insights in the mechanisms of interleukin-1beta stimulation of osteoprotegerin in osteoblast-like cells.

Unlabelled: The mechanisms of IL-1beta stimulation of OPG were studied in more detail. Whereas p38 and ERK activation was confirmed to be needed, NF-kappaB was not necessary for this regulation. We also found that OPG production after IL-1beta stimulation was not sufficient to block TRAIL-induced apoptosis in MG-63 cells.

Interleukin-6 receptor shedding is enhanced by interleukin-1beta and tumor necrosis factor alpha and is partially mediated by tumor necrosis factor alpha-converting enzyme in osteoblast-like cells.

Objective: Interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) activation of gp130 represents an alternative pathway for osteoclast development in inflammatory conditions. The goal of the present study was to investigate changes in sIL-6R levels in response to the inflammatory cytokines IL-1beta and tumor necrosis factor alpha (TNFalpha) and to determine the role of TNFalpha-converting enzyme (TACE) in this process.

Methods: Levels of sIL-6R in the culture media of MG63 and SAOS-2 osteoblast-like cell lines after exposure to various agents were determined by immunoassay.

Functional analysis of AtHKT1 in Arabidopsis shows that Na(+) recirculation by the phloem is crucial for salt tolerance.

Two allelic recessive mutations of Arabidopsis, sas2-1 and sas2-2, were identified as inducing sodium overaccumulation in shoots. The sas2 locus was found (by positional cloning) to correspond to the AtHKT1 gene. Expression in Xenopus oocytes revealed that the sas2-1 mutation did not affect the ionic selectivity of the transporter but strongly reduced the macro scopic (whole oocyte current) transport activity.