Fanny Comblain

Review of dietary supplements for the management of osteoarthritis in dogs in studies from 2004 to 2014

Osteoarthritis (OA) is a chronic, painful, degenerative and inflammatory disease that affects the synovial joints and leads finally to the loss of mobility. It is highly prevalent in dogs. Nowadays, no cure exists, and the pharmacological treatment is limited to clinical signs alleviation. Some positive beneficial effects have been highlighted with dietary supplements in the course of dog OA. The goals of this narrative review are to summarize the scientific data available in the literature on dietary supplements assessed in dog OA and to discuss some trails about how to improve several aspects of research and issues with dietary supplements, such as bioavailability and dosage regimen. Chondroitin sulphate, glucosamine, undenaturated type II collagen, avocado-soya bean unsaponifiables, curcumin and polyunsaturated fatty acids were studied in dog OA and therefore discussed in the present review. Most of them showed anticatabolic and anti-inflammatory effects. Unfortunately, few data exist concerning their pharmacokinetics. Their bioavailability is low, but new formulations are developed to enhance their gastrointestinal absorption. The clinical relevance of these new formulations compared to native forms should be demonstrated in good clinical trials. Even if further investigations are needed, dietary supplements should be considered in OA management.

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. Viscosupplementation is a process that aims to restore the normal rheological properties of synovial fluid. For the past years, hyaluronic acid was usually used but this molecule has some limitations including the short residency time in joint cavity. Recently, in vitro studies have suggested that chitosan could promote the expression of cartilage matrix components and reduce inflammatory and catabolic mediators production by chondrocytes. In vivo, chitosan prevented cartilage degradation and synovial membrane inflammation in OA induced rabbit model. Several studies have also shown that chitosan could induce chondrogenic differentiation of mesenchymal stem cells. Therefore, chitosan is an interesting polymer to design scaffold and hydrogel for cartilage lesion repair, cells transplantation, sustained drug release and viscosupplementation.

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. mRNA of the more differentially secreted proteins were quantified by RT-PCR in cell culture from 5 other patients. Finally, osteomodulin and fibulin-3 sequences were quantified by western blot and immunoassays in serum and culture supernatants. Results 175 proteins were identified in NSC osteoblast secretome. Data are available via ProteomeXchange with identifier PXD008494. Compared to NSC osteoblast secretome, 12 proteins were significantly less secreted (Osteomodulin, IGFBP5, VCAM-1, IGF2, 78 kDa glucose-regulated protein, versican, calumenin, IGFBP2, thrombospondin-4, periostin, reticulocalbin 1 and osteonectin), and 13 proteins were significantly more secreted by SC osteoblasts (CHI3L1, fibulin-3, SERPINE2, IGFBP6, SH3BGRL3, SERPINE1, reticulocalbin3, alpha-2-HS-glycoprotein, TIMP-2, IGFBP3, TIMP-1, SERPINF1, CSF-1). Similar changes in osteomodulin, IGF2, SERPINE1, fibulin-3 and CHI3L1 mRNA levels were observed. ELISAs assays confirm the decrease by half of osteomodulin protein in SC osteoblasts supernatant compared to NSC and in OA patients serum compared to healthy subjects. Fibulin-3 epitopes Fib3-1, Fib3-2 and Fib3-3 were also increased in SC osteoblasts supernatant compared to NSC. Conclusions We highlighted some proteins differentially secreted by the osteoblasts coming from OA subchondral bone sclerosis. These changes contribute to explain some features observed in OA subchondral bone, like the increase of bone remodeling or abnormalities in bone matrix mineralization. Among identified proteins, osteomodulin was found decreased and fibulin-3 increased in serum of OA patients. These findings suggest that osteomodulin and fibulin-3 fragments could be biomarkers to monitor early changes in subchondral bone metabolism in OA.

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. Primary human chondrocytes were cultured in monolayer until confluence and then incubated for 24 or 48 hours in the absence or in the presence of human interleukin(IL)-1β (10-11M) and with or without COT, each compound at the concentration of 4 μg/ml. Microarray gene expression profiling between control, COT, IL-1β and COT IL-1β conditions was performed. Immunoassays were used to confirm the effect of COT at the protein level. Results More than 4000 genes were differentially expressed between conditions. The key regulated pathways were related to inflammation, cartilage metabolism and angiogenesis. The IL-1β stimulated chemokine ligand 6, matrix metalloproteinase-13, bone morphogenetic protein-2 and stanniocalcin1 gene expressions and protein productions were down-regulated by COT. COT significantly decreased stanniocalcin1 production in basal condition. Serpin E1 gene expression and protein production were down-regulated by IL-1β. COT reversed the inhibitory effect of IL-1β. Serpin E1 gene expression was up-regulated by COT in control condition. Conclusion The COT mixture has beneficial effect on osteoarthritis physiopathology by regulating the synthesis of key catabolic, inflammatory and angiogenesis factors. These findings give a scientific rationale for the use of these natural ingredients in the management of osteoarthritis.

SAT0060 Proteomic analysis of osteoblasts secretome provides new insights in mechanisms underlying osteoarthritis subchondral bone sclerosis

Background Osteoarthritis (OA) is characterised by cartilage degradation but also by other joint tissues modification like subchondral bone sclerosis Objectives In this study, we used a proteomic approach to compare secretome of osteoblasts isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone Methods Secretome was analysed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system. mRNA of the more differentially secreted proteins were then quantified by RT-PCR and the most relevant proteins identified using western-blotting and immunoassays Results 175 proteins were identified in NSC osteoblasts secretome. Compared to NSC osteoblasts secretome, 13 proteins were significantly less secreted (Osteomodulin, CSF-1, IGFBP5, VCAM-1, IGF2, 78 kDa glucose-regulated protein, versican, calumenin, IGFBP2, thrombospondin-4, periostin, reticulocalbin 1 and osteonectin), and 12 proteins significantly more secreted by SC osteoblasts (CHI3L1, fibulin-3, SERPINE2, IGFBP6, SH3BGRL3, SERPINE1, reticulocalbin3, alpha-2-HS-glycoprotein, TIMP-2, IGFBP3, TIMP-1, SERPINF1). Similar changes in periostin, osteomodulin, SERPINE1, IGFBP6, fibulin-3 and CHI3L1 mRNA levels were observed. Finally, osteomodulin and fibulin-3 specific sequences were quantified by western blot and immunoassays in serum and osteoblasts conditioned culture supernatants. Conclusions We highlighted some proteins differentially secreted by NSC and SC osteoblasts of OA subchondral bone sclerosis. These changes contribute to explain some features observed in OA subchondral bone, like the increase of bone remodelling or abnormalities in bone matrix mineralization. Among identified proteins, osteomodulin was found decreased and fibulin-3 increased in serum of OA patients. These findings suggest that osteomodulin and fibulin-3 fragments could be biomarkers to monitor early changes in subchondral bone metabolism in OA. Acknowledgements The D-Board project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement No. 3 05 815. Disclosure of Interest None declared

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. So an attractive alternative for monitoring OA is the measurement of biochemical markers in blood, urine, or synovial fluid, which could reflect metabolic changes in joint tissue and therefore disease onset and progression. Animal models are relevant to investigate the early stage of OA and metabolic changes occurring in joint tissues. The goal of this narrative review is to summarize the scientific data available in the literature on soluble biomarkers in animal models of OA. Design A literature search was conducted using the PubMed/Medline and Scopus databases between February 1995 and December 2015. All original articles, systematic and narrative reviews published in French or in English were considered. Results We summarized the data of 69 studies and proposed a classification scheme for OA biomarkers in animal studies, largely inspired by the BIPEDS classification. Conclusions Studies about biomarkers and animal models indicate that some markers could be valuable to monitor OA progression and assess therapeutic response in some animal models.

Étude de l’évolution de la pathologie arthrosique et des propriétés mécaniques du cartilage sur un modèle d’arthrose spontanée chez le cobaye Dunkin-Hartley

PE.Lu-016 Traduction en français du « Brief Illness Perceived Questionnaire » adapté aux patients lombalgiques et étude de ses qualités métrologiques C. Demoulin* (1) ; L. Duvallon (2) ; N. Roussel (3) ; F. Humblet (4) ; S. Bornheim (1) ; E. Harry (5) ; I. Salamun (6) ; A. Lambert (7) ; D. Koch (8) ; G. Mahieu (9) ; JM. Crielaard (10) ; M. Vanderthommen (1) ; O. Bruyere (4) (1) Département des sciences de la motricité et service de médecine de l’appareil locomoteur, Université de Liège et CHU de Liège, Liège, Belgique ; (2) Clinique du dos, CHU de Liège – Site Ourthe-Amblève, Esneux, Belgique ; (3) Department of rehabilitation sciences and physiotherapy, Universiteit Antwerpen, Anvers, Belgique ; (4) Département des sciences de la santé publique, Université de Liège, Liège, Belgique ; (5) Islv, Université de Liège, Liège, Belgique ; (6) Service d’algologie, CHU de Liège, Liège, Belgique ; (7) Département des langues et littératures française et romanes, Université de Liège, Liège, Belgique ; (8) Centre de la douleur, CHR de la Citadelle, Liège, Belgique ; (9) Unité du dos, CHU UCL Namur site de Sainte-Anne, Dinant, Belgique ; (10) Service de médecine de l’appareil locomoteur et département des sciences de la motricité, CHU de Liège et Université de Liège, Liège, Belgique *Auteur correspondant : christophe.demoulin@ulg.ac.be (C. Demoulin)