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Main research area

Osteoarthritis is the most common disease in the elderly. Indeed, 65% of people over 60 years of age have osteoarthritis. Despite the high prevalence of osteoarthritis, its pathophysiology is not clearly established, especially since osteoarthritis is a multifactorial disease. The initial definition of osteoarthritis as the degeneration of cartilage with cyclic inflammatory phases under the dependence of the synovial membrane (the membrane surrounding the joint) is somewhat simplistic. Indeed, it is now accepted that bone and in particular subchondral bone (bone under the cartilage) plays a role in the arthritic process.

One of the characteristics of osteoarthritis is an attempt to repair cartilage by chondrocytes (cartilage cells), but this repair fails, particularly under the influence of factors secreted by the synovial membrane and subchondral bone. These factors can concurrently increase cartilage degradation and decrease repair, but also cause chondrocytes to dedifferentiate and return to expressing genes normally found in growth plates (conjugation cartilage) or during bone repair (endochondral ossification). Among the different re-expressed genes are those of collagenase-3 (MMP-13) and galectin-3.

            One of the growth factors found in greater quantity in osteoarthritic cartilage is hepatocyte growth factor (HGF). However, its synthesis is restricted to osteoblasts (bone cells), which suggests a paracrine role of this factor. In addition, in human chondrocytes, this HGF stimulates the production of collagenase-3, which is involved in cartilage remodeling and destruction, via the mitogen-activated protein kinases (MAPK) pathway.

During their de-differentiation, osteoarthritic chondrocytes also express and produce larger quantities of galectin-3, which is a lectin with different functions depending on its intra- or extracellular distribution. Although osteoarthritic chondrocytes produce more galectin-3, they secrete only small amounts. However, its intracellular presence is beneficial for chondrocytes since animals deficient in galectin-3 develop more osteoarthritis than non-mutated animals. In addition, using in vitro experiments, galectin-3 has a protective role against chondrocyte death. These results highlight the role of galectin-3 in cartilage homeostasis. However, animals deficient in galectin-3 do not have subchondral bone abnormalities except in the induction of osteoarthritis by intra-articular injection of mono-iodoacetate. These results show that galectin-3 does not appear to be essential for bone homeostasis, but when bone is subjected to metabolic stress, the absence of intracellular galectin-3 is harmful.

In contrast, galectin-3 can be secreted by the synovial membrane during inflammatory phases. During the latter, the synovial membrane generates a specific structure called pannus that envelops the cartilage and bone. Galectin-3 secretion can therefore directly reach chondrocytes and osteoblasts. Using chondrocytes, galectin-3 induces the expression of two major enzymes involved in the degradation of proteoglycans, one of the major components of the cartilage matrix. Galectin-3 also stimulates the expression of type X collagen, another cartilage compound normally expressed in the growth plate. Incubation of arthrosic osteoblasts in the presence of galectin-3 decreases the expression of osteocalcin, which is a marker of terminal osteoblast differentiation. According to literature,a truncated form of galectin-3, capable of binding to galectin-3 ligands but without activating a cellular signal, does not have this effect. Several strategies in order to produce a Trc-gal-3, devoid of biological activities was developed in the lab. Unfortunately, all of them presented biological effects on osteoarthritic chondrocytes. Among the Trc-gal-3 forms developed, one was selected because it had enough affinity for lactose and a great solubility. Thanks to theses properties, this form is used to generate a new method of purification of recombinant proteins.

Journal articles23 documents

  • Jean-Baptiste Gross, Cecile Guillaume, Pascal Gegout-Pottie, Pascal Reboul, Jean-Yves Jouzeau, et al.. The infrapatellar fat pad induces inflammatory and degradative effects in articular cells but not through leptin or adiponectin.. Clinical and experimental rheumatology, Clinical and Experimental Rheumatology Sas, 2017, 35 (1), pp.53-60. ⟨hal-01532184⟩
  • A. Bianchi, M. Guibert, F. Cailotto, A. Gasser, N. Presle, et al.. Fibroblast Growth Factor 23 drives MMP13 expression in human osteoarthritic chondrocytes in a Klotho-independent manner. Osteoarthritis and Cartilage, Elsevier, 2016, 24 (11), pp.1961-1969. ⟨10.1016/j.joca.2016.06.003⟩. ⟨hal-01452316⟩
  • Arnaud Bianchi, D. Moulin, S. Hupont, M. Koufany, P. Netter, et al.. Oxidative stress-induced expression of HSP70 contributes to the inhibitory effect of 15d-PGJ(2) on inducible prostaglandin pathway in chondrocytes. Free Radical Biology and Medicine, Elsevier, 2014, 76, pp.114-126. ⟨10.1016/j.freeradbiomed.2014.07.028⟩. ⟨hal-01453217⟩
  • Laurent Calvier, Maria Miana, Pascal Reboul, Victoria Cachofeiro, Ernesto Martinez-Martinez, et al.. Galectin-3 mediates aldosterone-induced vascular fibrosis.. Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2013, 33 (1), pp.67-75. ⟨10.1161/ATVBAHA.112.300569⟩. ⟨hal-00812594⟩
  • J. Monfort, G. Tardif, P. Roughley, P. Reboul, C. Boileau, et al.. Identification of opticin, a member of the small leucine-rich repeat proteoglycan family, in human articular tissues: a novel target for MMP-13 in osteoarthritis. Osteoarthritis and Cartilage, Elsevier, 2008, 16 (7), pp.749 - 755. ⟨10.1016/j.joca.2007.11.007⟩. ⟨hal-01705873⟩
  • C. Boileau, P. Poirier, P Pelletier, M Guévremont, N Duval, et al.. Intracellular localisation of galectin-3 has a protective role in chondrocyte survival. Annals of the Rheumatic Diseases, BMJ Publishing Group, 2008, 67 (2), pp.175 - 181. ⟨10.1136/ard.2006.066514⟩. ⟨hal-01704462⟩
  • Christelle Boileau, Françoise Poirier, Jean-Pierre Pelletier, Mélanie Guévremont, Nicolas Duval, et al.. Intracellular localization of Galectin-3 has a protective role.. Annals of the Rheumatic Diseases, BMJ Publishing Group, 2007, Sous presse (?), ⟨10.1136/ard.2006.066514⟩. ⟨hal-00155185⟩
  • P. Lavigne, M. Benderdour, D. Lajeunesse, P. Reboul, Q. Shi, et al.. Subchondral and trabecular bone metabolism regulation in canine experimental knee osteoarthritis. Osteoarthritis and Cartilage, Elsevier, 2005, 13 (4), pp.310 - 317. ⟨10.1016/j.joca.2004.12.015⟩. ⟨hal-01705735⟩
  • Mélanie Guevremont, Johanne Martel-Pelletier, Christelle Boileau, Ft Liu, Michel Richard, et al.. Galectin-3 surface expression on human adult chondrocytes: a potential substrate for collagenase-3. Annals of the Rheumatic Diseases, BMJ Publishing Group, 2004, 63 (6), pp.636 - 643. ⟨10.1136/ard.2003.007229⟩. ⟨hal-01704652⟩
  • G. Tardif, M. Dupuis, P. Reboul, C.S Geng, J. Pelletier, et al.. Identification and differential expression of human collagenase-3 mRNA species derived from internal deletion, alternative splicing, and different polyadenylation and transcription initiation sites. Osteoarthritis and Cartilage, Elsevier, 2003, 11 (7), pp.524 - 537. ⟨10.1016/S1063-4584(03)00079-7⟩. ⟨hal-01705862⟩
  • Johanne Martel-Pelletier, Daniel Lajeunesse, Pascal Reboul, Jean-Pierre Pelletier. Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective non-steroidal anti-inflammatory drugs. Annals of the Rheumatic Diseases, BMJ Publishing Group, 2003, 62 (6), pp.501 - 509. ⟨10.1136/ard.62.6.501⟩. ⟨hal-01705863⟩
  • D Jovanovic, J Di Battista, J. Martel-Pelletier, P. Reboul, Y. He, et al.. Modulation of TIMP-1 synthesis by antiinflammatory cytokines and prostaglandin E2 in interleukin 17 stimulated human monocytes/macrophages.. Journal of Rheumatology, Journal of Rheumatology Publishing Company Limited, 2001, pp.712-8. ⟨hal-01705579⟩
  • J. Pelletier, J. Fernandes, J Jovanovic, P. Reboul, J. Martel-Pelletier. Chondrocyte death in experimental osteoarthritis is mediated by MEK 1/2 and p38 pathways: role of cyclooxygenase-2 and inducible nitric oxide synthase.. Journal of Rheumatology, Journal of Rheumatology Publishing Company Limited, 2001, pp.2509-19. ⟨hal-01705868⟩
  • G Tardif, P. Reboul, M. Dupuis, C. Geng, N Duval, et al.. Transforming growth factor-beta induced collagenase-3 production in human osteoarthritic chondrocytes is triggered by Smad proteins: cooperation between activator protein-1 and PEA-3 binding sites.. Journal of Rheumatology, Journal of Rheumatology Publishing Company Limited, 2001, pp.1631-9. ⟨hal-01705281⟩
  • J. Pelletier, D Lajeunesse, P. Reboul, F Mineau, J. Fernandes, et al.. Diacerein reduces the excess synthesis of bone remodeling factors by human osteoblast cells from osteoarthritic subchondral bone.. Journal of Rheumatology, Journal of Rheumatology Publishing Company Limited, 2001, pp.814-24. ⟨hal-01705289⟩
  • Kohei Notoya, Dragan Jovanovic, P. Reboul, Johanne Martel-Pelletier, François Mineau, et al.. The Induction of Cell Death in Human Osteoarthritis Chondrocytes by Nitric Oxide Is Related to the Production of Prostaglandin E 2 Via the Induction of Cyclooxygenase-2. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2000, 165 (6), pp.3402-3410. ⟨10.4049/jimmunol.165.6.3402⟩. ⟨hal-01705606⟩
  • M. Piperno, P. Reboul, M Hellio Le Graverand, M Peschard, M Annefeld, et al.. Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro. Osteoarthritis and Cartilage, Elsevier, 2000, 8 (3), pp.207 - 212. ⟨10.1053/joca.1999.0291⟩. ⟨hal-01705629⟩
  • Muriel Piperno, P. Reboul, Marie-Pierre Hellio Le Graverand, Mj Peschard, Marliese Annefeld, et al.. Osteoarthritic cartilage fibrillation is associated with a decrease in chondrocyte adhesion to fibronectin.. Osteoarthritis and Cartilage, Elsevier, 1998, 6 (6), pp.393-399. ⟨10.1053/joca.1998.0138⟩. ⟨hal-01705650⟩
  • M. Piperno, M Hellio Le Graverand, P. Reboul, M. Mathieu, M Tron, et al.. Phospholipase A2 activity in herniated lumbar discs. Clinical correlations and inhibition by piroxicam.. Spine, Lippincott, Williams & Wilkins, 1997, pp.2061-5. ⟨hal-01705664⟩
  • S Tavera, T Abribat, P. Reboul, S Doré, P Brazeau, et al.. IGF and IGF-binding protein system in the synovial fluid of osteoarthritic and rheumatoid arthritic patients.. Osteoarthritis and Cartilage, Elsevier, 1996, pp.263-74. ⟨hal-01705669⟩
  • P. Reboul, Jean-Pierre Pelletier, Ginette Tardif, Jean-Marie Cloutier, Johanne Martel-Pelletier. The New Collagenase, Collagenase-3, Is Expressed and Synthesized by Human Chondrocytes but not by Synoviocytes A Role in Osteoarthritis. Journal of Clinical Investigation, American Society for Clinical Investigation, 1996, 97 (9), pp.2011-2019. ⟨10.1172/JCI118636⟩. ⟨hal-01705146⟩
  • Ginette Tardif, Pascal Reboul, Jean-Pierre Pelletier, Changshan Geng, Jean-Marie Cloutier, et al.. Normal expression of type 1 insulin-like growth factor receptor by human osteoarthritic chondrocytes with increased expression and synthesis of insulin-like growth factor binding proteins.. Arthritis and Rheumatism, Wiley, 1996, 39 (6), pp.968-978. ⟨10.1002/art.1780390614⟩. ⟨hal-01705166⟩
  • P. Reboul, P George, P. Louisot, P. Broquet. Study of retinoic acid effect upon retinoic acid receptors beta (RAR-beta) in C6 cultured glioma cells.. Biochemistry and molecular biology international, 1995, pp.1097-105. 〈hal-01705678〉

Conference papers3 documents

  • Alexandre Kriznik, Melissa Yelehe-Okouma, Christophe Charron, Hortense Mazon, Hélène Le Cordier, et al.. Efficient new lectin-based affinity tag allowing simple, safe and low-cost recombinant protein purification. The 14th International Symposium on BioChromatography and Nanoseparations, May 2018, Bordeaux, France. 2018. 〈hal-01719814〉
  • J. Hablot, M. Koufany, P. Reboul, J.-Y. Jouzeau, D. Moulin. FRI0017 Pharmacological Blockade of CCR3 Reduces Collagen-Induced Arthritis Severity. Annual European Congress of Rheumatology (EULAR), 2016, Londres, United Kingdom. ANNALS OF THE RHEUMATIC DISEASES, 75 (Suppl 2), pp.431.3 - 432, 2016, 〈10.1136/annrheumdis-2016-eular.4069〉. 〈hal-01706984〉
  • N. Hafsia, F. Poirier, D. Delacour, Pascal Reboul, D. Côme, et al.. Galectin 3 exerts a protective role in a murine model of osteoarthritis. EULAR 2014, Jun 2014, Paris, France. Annals of the Rheumatic Disease, 73 (Supplément 2), pp.796, 2014. 〈hal-01511612〉

Book sections3 documents

  • Elie Abed, Pascal Reboul, Daniel Lajeunesse. Sirtuins as markers of bone disease: a focus on osteoarthritis and osteoporosis.. Professor Victor R. Preedy. Biomarkers in Disease: Methods, Discoveries and Applications, Springer publisher, pp.154-175, 2017, 978-94-007-7745-3. 〈10.1007/2F978-94-007-7745-3_41-1〉. 〈hal-01709897〉
  • Johanne Martel-Pelletier, Daniel Lajeunesse, Pascal Reboul, Jean-Pierre Pelletier. The role of subchondral bone in osteoarthritis. Leena Sharma & Francis Berenbaum. Osteoarthritis, first edition, Mosby Elsevier publisher, pp.15-32, 2007. 〈hal-01709917〉
  • Daniel Lajeunesse, P. Reboul. The role of bone in the development of osteoarthritis.. F Bronner and MC Farach-Carson. Bone and Osteoarthritis, 4, pp.19-39, 2007, Topics in Bone Biology. 〈hal-01710478〉

Patents1 document

  • Alexandre Kriznik, Pascal Reboul, Melissa Yelehe-Okouma. Method for the affinity purification of recombinant proteins based on the lectin affinity of the CRD of a Galectin. France, N° de brevet: WO2017194888. 2017. 〈hal-01872013〉